This page has only limited features, please log in for full access.

Prof. Anthony Jaworowski
School of Health and Biomedical Sciences, RMIT University, Melbourne, Australia

Basic Info

Basic Info is private.

Research Keywords & Expertise

0 HIV
0 Signal Transduction
0 Macrophage
0 NK cell
0 Monocyte

Fingerprints

HIV
Monocyte
Macrophage
NK cell
Signal Transduction

Honors and Awards

The user has no records in this section


Career Timeline

The user has no records in this section.


Short Biography

The user biography is not available.
Following
Followers
Co Authors
The list of users this user is following is empty.
Following: 0 users

Feed

Review
Published: 20 August 2021 in International Journal of Molecular Sciences
Reads 0
Downloads 0

While first and foremost considered a respiratory infection, COVID-19 can result in complications affecting multiple organs. Immune responses in COVID-19 can both protect against the disease as well as drive it. Insights into these responses, and specifically the targets being recognised by the immune system, are of vital importance in understanding the side effects of COVID-19 and associated pathologies. The body’s adaptive immunity recognises and responds against specific targets (antigens) expressed by foreign pathogens, but not usually to target self-antigens. However, if the immune system becomes dysfunctional, adaptive immune cells can react to self-antigens, which can result in autoimmune disease. Viral infections are well reported to be associated with, or exacerbate, autoimmune diseases such as multiple sclerosis (MS) and systemic lupus erythematosus (SLE). In COVID-19 patients, both new onset MS and SLE, as well as the occurrence of other autoimmune-like pathologies, have been reported. Additionally, the presence of autoantibodies, both with and without known associations to autoimmune diseases, have been found. Herein we describe the mechanisms of virally induced autoimmunity and summarise some of the emerging reports on the autoimmune-like diseases and autoreactivity that is reported to be associated with SARS-CoV-2 infection.

ACS Style

Rhiane Moody; Kirsty Wilson; Katie L. Flanagan; Anthony Jaworowski; Magdalena Plebanski. Adaptive Immunity and the Risk of Autoreactivity in COVID-19. International Journal of Molecular Sciences 2021, 22, 8965 .

AMA Style

Rhiane Moody, Kirsty Wilson, Katie L. Flanagan, Anthony Jaworowski, Magdalena Plebanski. Adaptive Immunity and the Risk of Autoreactivity in COVID-19. International Journal of Molecular Sciences. 2021; 22 (16):8965.

Chicago/Turabian Style

Rhiane Moody; Kirsty Wilson; Katie L. Flanagan; Anthony Jaworowski; Magdalena Plebanski. 2021. "Adaptive Immunity and the Risk of Autoreactivity in COVID-19." International Journal of Molecular Sciences 22, no. 16: 8965.

Journal article
Published: 20 August 2021 in Cancers
Reads 0
Downloads 0

Autoantibodies recognising phosphorylated heat shock factor 1 (HSF1-PO4) protein are suggested as potential new diagnostic biomarkers for early-stage high-grade serous ovarian cancer (HGSOC). We predicted in silico B-cell epitopes in human and murine HSF1. Three epitope regions were synthesised as peptides. Circulating immunoglobulin A (cIgA) against the predicted peptide epitopes or HSF1-PO4 was measured using ELISA, across two small human clinical trials of HGSOC patients at diagnosis. To determine whether chemotherapy would promote changes in reactivity to either HSF1-PO4 or the HSF-1 peptide epitopes, IgA responses were further assessed in a sample of patients after a full cycle of chemotherapy. Anti-HSF1-PO4 responses correlated with antibody responses to the three selected epitope regions, regardless of phosphorylation, with substantial cross-recognition of the corresponding human and murine peptide epitope variants. Assessing reactivity to individual peptide epitopes, compared to HSF1-PO4, improved assay sensitivity. IgA responses to HSF1-PO4 further increased significantly post treatment, indicating that HSF1-PO4 is a target for immunity in response to chemotherapy. Although performed in a small cohort, these results offer potential insights into the interplay between autoimmunity and ovarian cancer and offer new peptide biomarkers for early-stage HGSOC diagnosis, to monitor responses to chemotherapy, and widely for pre-clinical HGSOC research.

ACS Style

Rhiane Moody; Kirsty Wilson; Nirmala Chandralega Kampan; Orla M. McNally; Thomas W. Jobling; Anthony Jaworowski; Andrew N. Stephens; Magdalena Plebanski. Mapping Epitopes Recognised by Autoantibodies Shows Potential for the Diagnosis of High-Grade Serous Ovarian Cancer and Monitoring Response to Therapy for This Malignancy. Cancers 2021, 13, 4201 .

AMA Style

Rhiane Moody, Kirsty Wilson, Nirmala Chandralega Kampan, Orla M. McNally, Thomas W. Jobling, Anthony Jaworowski, Andrew N. Stephens, Magdalena Plebanski. Mapping Epitopes Recognised by Autoantibodies Shows Potential for the Diagnosis of High-Grade Serous Ovarian Cancer and Monitoring Response to Therapy for This Malignancy. Cancers. 2021; 13 (16):4201.

Chicago/Turabian Style

Rhiane Moody; Kirsty Wilson; Nirmala Chandralega Kampan; Orla M. McNally; Thomas W. Jobling; Anthony Jaworowski; Andrew N. Stephens; Magdalena Plebanski. 2021. "Mapping Epitopes Recognised by Autoantibodies Shows Potential for the Diagnosis of High-Grade Serous Ovarian Cancer and Monitoring Response to Therapy for This Malignancy." Cancers 13, no. 16: 4201.

Short communication
Published: 05 May 2021 in Antiviral Research
Reads 0
Downloads 0

HIV-infected macrophages contribute to persistence of HIV reservoirs in people living with HIV receiving antiretroviral therapy. A potential strategy to eliminate reservoirs is the use of antibody-dependent cellular cytotoxicity (ADCC) against infected cells expressing the HIV envelope (Env) protein on their surface. Designing ADCC strategies requires knowledge of exposed Env epitopes on the cell surface and identifying antibodies capable of opsonising infected cells, yet little is known regarding the ability of HIV-infected macrophages to be targeted with such strategies. Using a panel of neutralising and poorly-neutralising anti-Env antibodies we compared Env epitopes expressed on infected monocyte-derived macrophages (MDM) and autologous T cells. Our results reveal potential differences in epitope expression on macrophage- and T cell-expressed Env. Notably, HIVBaL-infected macrophages were more susceptible to opsonisation by NIH45-46 (median = 40.4%) compared to infected T cells (13.6%; p = 0.002), which were more susceptible to opsonisation by 17b and 447.52D (88.6% and 45.6% respectively) compared to MDM (30% and 6.7%, p = 0.002 and 0.004 respectively). Furthermore, neutralising antibodies 10E8 and PGT145 were relatively ineffective at opsonising Env expressed on the surface of infected T cells or macrophages, indicating that the context in which Env is presented on infected cells may differ to that of cell-free virions.

ACS Style

Hans Kek; Annemarie Laumaea; Srihari Parise; Pantelis Poumbourios; Anna C. Hearps; Anthony Jaworowski. Differential expression of HIV envelope epitopes on the surface of HIV-Infected macrophages and CD4+ T cells. Antiviral Research 2021, 191, 105085 .

AMA Style

Hans Kek, Annemarie Laumaea, Srihari Parise, Pantelis Poumbourios, Anna C. Hearps, Anthony Jaworowski. Differential expression of HIV envelope epitopes on the surface of HIV-Infected macrophages and CD4+ T cells. Antiviral Research. 2021; 191 ():105085.

Chicago/Turabian Style

Hans Kek; Annemarie Laumaea; Srihari Parise; Pantelis Poumbourios; Anna C. Hearps; Anthony Jaworowski. 2021. "Differential expression of HIV envelope epitopes on the surface of HIV-Infected macrophages and CD4+ T cells." Antiviral Research 191, no. : 105085.

Original research article
Published: 22 September 2020 in Journal of Cellular Physiology
Reads 0
Downloads 0

Mechanosensitive ion channels mediate endothelial responses to blood flow and orchestrate their physiological function in response to hemodynamic forces. In this study, we utilized microfluidic technologies to study the shear‐induced sensitization of endothelial Piezo‐1 to its selective agonist, Yoda‐1. We demonstrated that shear stress‐induced sensitization is brief and can be impaired when exposing aortic endothelial cells to low and proatherogenic levels of shear stress. Our results suggest that shear stress‐induced sensitization of Piezo‐1 to Yoda‐1 is independent of cell–cell adhesion and is mediated by the PI3K‐AKT signaling pathway. We also found that shear stress increases the membrane density of Piezo‐1 channels in endothelial cells. To further confirm our findings, we performed experiments using a carotid artery ligation mouse model and demonstrated that transient changes in blood‐flow pattern, resulting from a high‐degree ligation of the mouse carotid artery alters the distribution of Piezo‐1 channels across the endothelial layer. These results suggest that shear stress influences the function of Piezo‐1 channels via changes in membrane density, providing a new model of shear‐stress sensitivity for Piezo‐1 ion channel.

ACS Style

Austin Lai; Yung C. Chen; Charles D. Cox; Anthony Jaworowski; Karlheinz Peter; Sara Baratchi. Analyzing the shear‐induced sensitization of mechanosensitive ion channel Piezo‐1 in human aortic endothelial cells. Journal of Cellular Physiology 2020, 236, 2976 -2987.

AMA Style

Austin Lai, Yung C. Chen, Charles D. Cox, Anthony Jaworowski, Karlheinz Peter, Sara Baratchi. Analyzing the shear‐induced sensitization of mechanosensitive ion channel Piezo‐1 in human aortic endothelial cells. Journal of Cellular Physiology. 2020; 236 (4):2976-2987.

Chicago/Turabian Style

Austin Lai; Yung C. Chen; Charles D. Cox; Anthony Jaworowski; Karlheinz Peter; Sara Baratchi. 2020. "Analyzing the shear‐induced sensitization of mechanosensitive ion channel Piezo‐1 in human aortic endothelial cells." Journal of Cellular Physiology 236, no. 4: 2976-2987.

Research article
Published: 15 September 2020 in Circulation
Reads 0
Downloads 0

Background: Aortic valve stenosis is an increasingly prevalent degenerative and inflammatory disease. Transcatheter aortic valve implantation (TAVI) has revolutionized its treatment, thereby avoiding its life-threatening/disabling consequences. Whether aortic valve stenosis is accelerated by inflammation and whether it is itself a cause of inflammation are unclear. We hypothesized that the large shear forces exerted on circulating cells, particularly on the largest circulating cells, monocytes, while passing through stenotic aortic valves result in proinflammatory effects that are resolved with TAVI. Methods: TAVI provides a unique opportunity to compare the activation status of monocytes under high shear stress (before TAVI) and under low shear stress (after TAVI). The activation status of monocytes was determined with a single-chain antibody, MAN-1, which is specific for the activated β 2 -integrin Mac-1. Monocyte function was further characterized by the adhesion of myocytes to stimulated endothelial cells, phagocytic activity, uptake of oxidized low-density lipoprotein, and cytokine expression. In addition, we designed a microfluidic system to recapitulate the shear rate conditions before and after TAVI. We used this tool in combination with functional assays, Ca 2+ imaging, siRNA gene silencing, and pharmacological agonists and antagonists to identify the key mechanoreceptor mediating the shear stress sensitivity of monocytes. Last, we stained for monocytes in explanted stenotic aortic human valves. Results: The resolution of high shear stress through TAVI reduces Mac-1 activation, cellular adhesion, phagocytosis, oxidized low-density lipoprotein uptake, and expression of inflammatory markers in monocytes and plasma. Using microfluidics and pharmacological and genetic studies, we could recapitulate high shear stress effects on isolated human monocytes under highly controlled conditions, showing that shear stress–dependent calcium influx and monocyte adhesion are mediated by the mechanosensitive ion channel Piezo-1. We also demonstrate that the expression of this receptor is shear stress dependent and downregulated in patients receiving TAVI. Last, we show monocyte accumulation at the aortic side of leaflets of explanted aortic valves. Conclusions: We demonstrate that high shear stress, as present in patients with aortic valve stenosis, activates multiple monocyte functions, and we identify Piezo-1 as the mainly responsible mechanoreceptor, representing a potentially druggable target. We demonstrate an anti-inflammatory effect and therefore a novel therapeutic benefit of TAVI.

ACS Style

Sara Baratchi; Maria T.K. Zaldivia; Maria Wallert; Julia Loseff-Silver; Sefaa Al-Aryahi; Jalal Zamani; Peter Thurgood; Agus Salim; Nay M. Htun; Dion Stub; Parisa Vahidi; Stephen J. Duffy; Antony Walton; Thanh Ha Nguyen; Anthony Jaworowski; Khashayar Khoshmanesh; Karlheinz Peter. Transcatheter Aortic Valve Implantation Represents an Anti-Inflammatory Therapy Via Reduction of Shear Stress–Induced, Piezo-1–Mediated Monocyte Activation. Circulation 2020, 142, 1092 -1105.

AMA Style

Sara Baratchi, Maria T.K. Zaldivia, Maria Wallert, Julia Loseff-Silver, Sefaa Al-Aryahi, Jalal Zamani, Peter Thurgood, Agus Salim, Nay M. Htun, Dion Stub, Parisa Vahidi, Stephen J. Duffy, Antony Walton, Thanh Ha Nguyen, Anthony Jaworowski, Khashayar Khoshmanesh, Karlheinz Peter. Transcatheter Aortic Valve Implantation Represents an Anti-Inflammatory Therapy Via Reduction of Shear Stress–Induced, Piezo-1–Mediated Monocyte Activation. Circulation. 2020; 142 (11):1092-1105.

Chicago/Turabian Style

Sara Baratchi; Maria T.K. Zaldivia; Maria Wallert; Julia Loseff-Silver; Sefaa Al-Aryahi; Jalal Zamani; Peter Thurgood; Agus Salim; Nay M. Htun; Dion Stub; Parisa Vahidi; Stephen J. Duffy; Antony Walton; Thanh Ha Nguyen; Anthony Jaworowski; Khashayar Khoshmanesh; Karlheinz Peter. 2020. "Transcatheter Aortic Valve Implantation Represents an Anti-Inflammatory Therapy Via Reduction of Shear Stress–Induced, Piezo-1–Mediated Monocyte Activation." Circulation 142, no. 11: 1092-1105.

Research article
Published: 29 July 2020 in PLOS ONE
Reads 0
Downloads 0

Malaria in pregnancy causes maternal, fetal and neonatal morbidity and mortality, and maternal innate immune responses are implicated in pathogenesis of these complications. The effects of malaria exposure and obstetric and demographic factors on the early maternal immune response are poorly understood. Peripheral blood mononuclear cell responses to Plasmodium falciparum-infected erythrocytes and phytohemagglutinin were compared between pregnant women from Papua New Guinea (malaria-exposed) with and without current malaria infection and from Australia (unexposed). Elicited levels of inflammatory cytokines at 48 h and 24 h (interferon γ, IFN-γ only) and the cellular sources of IFN-γ were analysed. Among Papua New Guinean women, microscopic malaria at enrolment did not alter peripheral blood mononuclear cell responses. Compared to samples from Australia, cells from Papua New Guinean women secreted more inflammatory cytokines tumor necrosis factor-α, interleukin 1β, interleukin 6 and IFN-γ; p<0.001 for all assays, and more natural killer cells produced IFN-γ in response to infected erythrocytes and phytohemagglutinin. In both populations, cytokine responses were not affected by gravidity, except that in the Papua New Guinean cohort multigravid women had higher IFN-γ secretion at 24 h (p = 0.029) and an increased proportion of IFN-γ+ Vδ2 γδ T cells (p = 0.003). Cytokine levels elicited by a pregnancy malaria-specific CSA binding parasite line, CS2, were broadly similar to those elicited by CD36-binding line P6A1. Geographic location and, to some extent, gravidity influence maternal innate immunity to malaria.

ACS Style

Marzieh Jabbarzare; Madi Njie; Anthony Jaworowski; Alexandra J. Umbers; Maria Ome-Kaius; Wina Hasang; Louise M. Randall; Bill Kalionis; Stephen J. Rogerson. Innate immune responses to malaria-infected erythrocytes in pregnant women: Effects of gravidity, malaria infection, and geographic location. PLOS ONE 2020, 15, e0236375 .

AMA Style

Marzieh Jabbarzare, Madi Njie, Anthony Jaworowski, Alexandra J. Umbers, Maria Ome-Kaius, Wina Hasang, Louise M. Randall, Bill Kalionis, Stephen J. Rogerson. Innate immune responses to malaria-infected erythrocytes in pregnant women: Effects of gravidity, malaria infection, and geographic location. PLOS ONE. 2020; 15 (7):e0236375.

Chicago/Turabian Style

Marzieh Jabbarzare; Madi Njie; Anthony Jaworowski; Alexandra J. Umbers; Maria Ome-Kaius; Wina Hasang; Louise M. Randall; Bill Kalionis; Stephen J. Rogerson. 2020. "Innate immune responses to malaria-infected erythrocytes in pregnant women: Effects of gravidity, malaria infection, and geographic location." PLOS ONE 15, no. 7: e0236375.

Article
Published: 15 March 2020 in AIDS
Reads 0
Downloads 0

People living with HIV have an increased risk of cardiovascular disease (CVD) despite effective antiretroviral therapy (ART). Monocytes play a key role in the early stages of atherosclerosis-driven CVD by forming lipid-laden foam cells within artery walls. HIV infection potentiates foam cell formation ex vivo, but the mechanisms contributing to this are not known. We investigated the atherosclerosis-promoting potential of monocytes from 39 virologically suppressed men living with HIV (MLHIV) on ART and no evidence of CVD, and 25 HIV-uninfected controls of comparable age, sex, smoking status and CVD risk. Despite absence of clinical atherosclerosis in both MLHIV and uninfected cohorts (evidenced by a carotid intima-media thickness of 0.6 mm for both groups; p = 0.254), monocytes from MLHIV showed increased potential to form atherosclerosis-promoting foam cells compared to controls in an ex vivo assay (36.6% vs 27.6% respectively, p = 0.003). Consistent with observations of persistent inflammation and immune/endothelial activation in ART-treated HIV infection, levels of soluble TNF receptor II, CXCL10 and soluble VCAM-1 were elevated in MLHIV (p≤0.005 for all), but were not significantly associated with foam cell formation. Foam cell formation was associated with an impaired ability of monocytes to undergo reverse transmigration, and a reduced ability to efflux cholesterol ex vivo (p These findings highlight the persistence of HIV-related changes to the atherogenic potential of monocytes despite long-term viral suppression, and provide insights into mechanisms potentially driving increased CVD in ART-treated HIV infection.

ACS Style

Thomas Angelovich; Janine M. Trevillyan; Jennifer F. Hoy; Michelle E. Wong; Paul Agius; Anna C. Hearps; Anthony Jaworowski. Monocytes from men living with HIV exhibit heightened atherogenic potential despite long-term viral suppression with antiretroviral therapy. AIDS 2020, 34, 513 -518.

AMA Style

Thomas Angelovich, Janine M. Trevillyan, Jennifer F. Hoy, Michelle E. Wong, Paul Agius, Anna C. Hearps, Anthony Jaworowski. Monocytes from men living with HIV exhibit heightened atherogenic potential despite long-term viral suppression with antiretroviral therapy. AIDS. 2020; 34 (4):513-518.

Chicago/Turabian Style

Thomas Angelovich; Janine M. Trevillyan; Jennifer F. Hoy; Michelle E. Wong; Paul Agius; Anna C. Hearps; Anthony Jaworowski. 2020. "Monocytes from men living with HIV exhibit heightened atherogenic potential despite long-term viral suppression with antiretroviral therapy." AIDS 34, no. 4: 513-518.

Review
Published: 13 March 2020 in Cancers
Reads 0
Downloads 0

Cancer-related deaths are approaching 10 million each year. Survival statistics for some cancers, such as ovarian cancer, have remained unchanged for decades, with women diagnosed at stage III or IV having over 80% chance of a lethal cancer recurrence after standard first-line treatment (reductive surgery and chemotherapy). New treatments and adjunct therapies are needed. In ovarian cancer, as in other cancers, the immune response, particularly cytotoxic (CD8+) T cells are correlated with a decreased risk of recurrence. As well as completely new antigen targets resulting from DNA mutations (neo-antigens), these T cells recognize cancer-associated overexpressed, re-expressed or modified self-proteins. However, there is concern that activation of self-reactive responses may also promote off-target pathology. This review considers the complex interplay between cancer-reactive and self-reactive immune cells and discusses the potential uses for various leading immunomodulatory compounds, derived from plant-based sources, as a cancer therapy option or to modulate potential autoimmune pathology. Along with reviewing well-studied compounds such as curcumin (from turmeric), epigallocatechin gallate (EGCG, from green tea) and resveratrol (from grapes and certain berries), it is proposed that compounds from novel sources, for example, native Australian plants, will provide a useful source for the fine modulation of cancer immunity in patients.

ACS Style

Rhiane Moody; Kirsty Wilson; Anthony Jaworowski; Magdalena Plebanski. Natural Compounds with Potential to Modulate Cancer Therapies and Self-Reactive Immune Cells. Cancers 2020, 12, 673 .

AMA Style

Rhiane Moody, Kirsty Wilson, Anthony Jaworowski, Magdalena Plebanski. Natural Compounds with Potential to Modulate Cancer Therapies and Self-Reactive Immune Cells. Cancers. 2020; 12 (3):673.

Chicago/Turabian Style

Rhiane Moody; Kirsty Wilson; Anthony Jaworowski; Magdalena Plebanski. 2020. "Natural Compounds with Potential to Modulate Cancer Therapies and Self-Reactive Immune Cells." Cancers 12, no. 3: 673.

Immunology
Published: 22 October 2019 in Frontiers in Immunology
Reads 0
Downloads 0

Corrigendum: The HIV Reservoir in Monocytes and Macrophages

ACS Style

Michelle E. Wong; Anthony Jaworowski; Anna C. Hearps. Corrigendum: The HIV Reservoir in Monocytes and Macrophages. Frontiers in Immunology 2019, 10, 1 .

AMA Style

Michelle E. Wong, Anthony Jaworowski, Anna C. Hearps. Corrigendum: The HIV Reservoir in Monocytes and Macrophages. Frontiers in Immunology. 2019; 10 ():1.

Chicago/Turabian Style

Michelle E. Wong; Anthony Jaworowski; Anna C. Hearps. 2019. "Corrigendum: The HIV Reservoir in Monocytes and Macrophages." Frontiers in Immunology 10, no. : 1.

Research article
Published: 10 October 2019 in PLOS ONE
Reads 0
Downloads 0

Malaria is responsible for almost half a million deaths annually. The role of Vγ9Vδ2 γδ T cells in malaria is still unclear. Studies have reported an association between this cell subset and malaria symptoms and severity. Profiles of Vγ9Vδ2 γδ T cells in bigger cohorts with different levels of clinical severity have not been described. Proportion, numbers, and activation status of Vγ9Vδ2 γδ T cells were measured by flow cytometry in 59 healthy controls (HCs), 58 children with uncomplicated malaria (UM) and 67 with cerebral malaria (CM,) during acute malaria and in convalescence 28 days later. Vγ9Vδ2 γδ T cell were lower in children presenting with UM and CM than in HCs. Cell counts did not vary with malaria severity (CM median counts 40 x 103 cells/μL, IQR [23-103]; UM median counts 30 x 103 cells/μL [10-90], P = 0.224). Vγ9Vδ2 γδ T cell counts increased during convalescence for UM (70 [40-60] x 103 cells/μL and CM (90 [60-140] x 103 cells/μL), to levels similar to those in HCs (70 [50-140] x 103 cells/μL), p = 0.70 and p = 0.40 respectively. Expression of the activation markers CD69 and HLA-DR on Vγ9Vδ2 γδ T cells was higher in malaria cases than in controls (HCs vs UM or CM, p < 0.0001) but was similar between UM and CM. HLA-DR expression remained elevated at 28 days, suggesting sustained activation of Vγ9Vδ2 γδ T cells during recovery. Vγ9Vδ2 γδ T cell proportions and cells counts were suppressed in acute disease and normalized in convalescence, a phenomenon previously hypothesized to be due to transient migration of the cells to secondary lymphoid tissue. The presence of highly activated Vγ9Vδ2 γδ T cells suggests that this T cell subset plays a specific role in response to malaria infection.

ACS Style

Visopo Harawa; Madi Njie; Thomas Keller; Kami Kim; Anthony Jaworowski; Karl Seydel; Stephen J. Rogerson; Wilson Mandala. Malawian children with uncomplicated and cerebral malaria have decreased activated Vγ9Vδ2 γδ T cells which increase in convalescence. PLOS ONE 2019, 14, e0223410 .

AMA Style

Visopo Harawa, Madi Njie, Thomas Keller, Kami Kim, Anthony Jaworowski, Karl Seydel, Stephen J. Rogerson, Wilson Mandala. Malawian children with uncomplicated and cerebral malaria have decreased activated Vγ9Vδ2 γδ T cells which increase in convalescence. PLOS ONE. 2019; 14 (10):e0223410.

Chicago/Turabian Style

Visopo Harawa; Madi Njie; Thomas Keller; Kami Kim; Anthony Jaworowski; Karl Seydel; Stephen J. Rogerson; Wilson Mandala. 2019. "Malawian children with uncomplicated and cerebral malaria have decreased activated Vγ9Vδ2 γδ T cells which increase in convalescence." PLOS ONE 14, no. 10: e0223410.

Review article
Published: 26 June 2019 in Frontiers in Immunology
Reads 0
Downloads 0

In people living with HIV (PLWH) who are failing or unable to access combination antiretroviral therapy (cART), monocytes and macrophages are important drivers of pathogenesis and progression to AIDS. The relevance of the monocyte/macrophage reservoir in PLWH receiving cART is debatable as in vivo evidence for infected cells is limited and suggests the reservoir is small. Macrophages were assumed to have a moderate life span and lack self-renewing potential, but recent discoveries challenge this dogma and suggest a potentially important role of these cells as long-lived HIV reservoirs. This, combined with new HIV infection animal models, has led to a resurgence of interest in monocyte/macrophage reservoirs. Infection of non-human primates with myeloid-tropic SIV implicates monocyte/macrophage activation and infection in the brain with neurocognitive disorders, and infection of myeloid-only humanized mouse models are consistent with the potential of the monocyte/macrophage reservoir to sustain infection and be a source of rebound viremia following cART cessation. An increased resistance to HIV-induced cytopathic effects and a reduced susceptibility to some antiretroviral drugs implies macrophages may be relevant to residual replication under cART and to rebound viremia. With a reappraisal of monocyte circulation dynamics, and the development of techniques to differentiate between self-renewing tissue-resident, and monocyte-derived macrophages in different tissues, a new framework exists to contextualize and evaluate the significance and relevance of the monocyte/macrophage HIV reservoir. In this review, we discuss recent developments in monocyte and macrophage biology and appraise current and emerging techniques to quantify the reservoir. We discuss how this knowledge influences our evaluation of the myeloid HIV reservoir, the implications for HIV pathogenesis in both viremic and virologically-suppressed PLWH and the need to address the myeloid reservoir in future treatment and cure strategies.

ACS Style

Michelle E. Wong; Anthony Jaworowski; Anna C. Hearps. The HIV Reservoir in Monocytes and Macrophages. Frontiers in Immunology 2019, 10, 1435 .

AMA Style

Michelle E. Wong, Anthony Jaworowski, Anna C. Hearps. The HIV Reservoir in Monocytes and Macrophages. Frontiers in Immunology. 2019; 10 ():1435.

Chicago/Turabian Style

Michelle E. Wong; Anthony Jaworowski; Anna C. Hearps. 2019. "The HIV Reservoir in Monocytes and Macrophages." Frontiers in Immunology 10, no. : 1435.

Review article
Published: 19 June 2019 in Frontiers in Immunology
Reads 0
Downloads 0

Combination antiretroviral therapy (ART) is effective at suppressing HIV viremia to achieve persistently undetectable levels in peripheral blood in the majority of individuals with access and ability to maintain adherence to treatment. However, evidence suggests that ART is less effective at eliminating HIV-associated inflammation and innate immune activation. To the extent that residual inflammation and immune activation persist, virologically suppressed people living with HIV (PLWH) may have increased risk of inflammatory co-morbidities, and adjunctive therapies may need to be considered to reduce HIV-related inflammation and fully restore the health of virologically suppressed HIV+ individuals. Cardiovascular disease (CVD) is the single leading cause of death in the developed world and is becoming more important in PLWH with access to ART. Arterial disease due to atherosclerosis, leading to acute myocardial infarction (AMI) and stroke, is a major component of CVD. Atherosclerosis is an inflammatory disease, and epidemiological comparisons of atherosclerosis and AMI show a higher prevalence and suggest a greater risk in PLWH compared to the general population. The reasons for greater prevalence of CVD in PLWH can be broadly grouped into four categories: (a) the higher prevalence of traditional risk factors e.g., smoking and hypertension (b) dyslipidemia (also a traditional risk factor) caused by off-target effects of ART drugs (c) HIV-related inflammation and immune activation and (d) other undefined HIV-related factors. Management strategies aimed at reducing the impact of traditional risk factors in PLWH are similar to those for the general population and their effectiveness is currently being evaluated. Together with improvements in ART regimens and guidelines for treatment, and a greater awareness of its impact on CVD, the HIV-related risk of AMI and stroke is decreasing but remains elevated compared to the general community. Monocytes are key effector cells which initiate the formation of atherosclerotic plaques by migrating into the intima of coronary arteries and accumulating as foam cells full of lipid droplets. This review considers the specific role of monocytes as effector cells in atherosclerosis which progresses to AMI and stroke, and explores mechanisms by which HIV may promote an atherogenic phenotype and function independent of traditional risk factors. Altered monocyte function may represent a distinct HIV-related factor which increases risk of CVD in PLWH.

ACS Style

Anthony Jaworowski; Anna C. Hearps; Thomas Angelovich; Jennifer F. Hoy. How Monocytes Contribute to Increased Risk of Atherosclerosis in Virologically-Suppressed HIV-Positive Individuals Receiving Combination Antiretroviral Therapy. Frontiers in Immunology 2019, 10, 1378 .

AMA Style

Anthony Jaworowski, Anna C. Hearps, Thomas Angelovich, Jennifer F. Hoy. How Monocytes Contribute to Increased Risk of Atherosclerosis in Virologically-Suppressed HIV-Positive Individuals Receiving Combination Antiretroviral Therapy. Frontiers in Immunology. 2019; 10 ():1378.

Chicago/Turabian Style

Anthony Jaworowski; Anna C. Hearps; Thomas Angelovich; Jennifer F. Hoy. 2019. "How Monocytes Contribute to Increased Risk of Atherosclerosis in Virologically-Suppressed HIV-Positive Individuals Receiving Combination Antiretroviral Therapy." Frontiers in Immunology 10, no. : 1378.

Journal article
Published: 26 November 2018 in Malaria Journal
Reads 0
Downloads 0

Cerebral malaria (CM) is often fatal, and severe brain swelling is a predictor of CM-related mortality. CM is characterized by elevated circulating pro-inflammatory cytokines TNF and IFN-γ and anti-inflammatory cytokine IL-10, however whether cytokine levels correlate with brain swelling severity is unknown. This study therefore was conducted to investigate the relationship between cytokine levels and brain swelling severity in children presenting with CM. A total of 195 Malawian children presenting with CM were recruited and had the concentrations of plasma cytokines determined and compared to brain swelling severity, determined by MRI examination, and graded as severe, moderate, mild or none. Levels of IL-1β, IL-6, IL-8 and IL-10 did not differ between CM patients with and without severe brain swelling. Compared to children without brain swelling, IL-12 levels were higher in children with severe swelling (p < 0.01, no swelling 1 pg/mL, IQR [1] vs. severe swelling 18.7 pg/mL, IQR [1-27]), whereas TNF concentrations were higher in children with moderate brain swelling compared to children with no swelling (p < 0.01, no swelling 3 pg/mL, IQR [1-20] vs. moderate swelling 24 pg/mL, IQR [8-58]. Multivariate analysis showed that no single cytokine independently predicted brain swelling. Severe brain swelling in paediatric CM was independent of tested blood pro-inflammatory and anti-inflammatory cytokines which are markers of systemic inflammation.

ACS Style

Visopo Harawa; Madi Njie; Anne Kessler; Augustine Choko; Benjamin Kumwenda; Sam Kampondeni; Michael Potchen; Kami Kim; Anthony Jaworowski; Terrie Taylor; Wilson Mandala; Karl Seydel; Stephen Rogerson. Brain swelling is independent of peripheral plasma cytokine levels in Malawian children with cerebral malaria. Malaria Journal 2018, 17, 435 .

AMA Style

Visopo Harawa, Madi Njie, Anne Kessler, Augustine Choko, Benjamin Kumwenda, Sam Kampondeni, Michael Potchen, Kami Kim, Anthony Jaworowski, Terrie Taylor, Wilson Mandala, Karl Seydel, Stephen Rogerson. Brain swelling is independent of peripheral plasma cytokine levels in Malawian children with cerebral malaria. Malaria Journal. 2018; 17 (1):435.

Chicago/Turabian Style

Visopo Harawa; Madi Njie; Anne Kessler; Augustine Choko; Benjamin Kumwenda; Sam Kampondeni; Michael Potchen; Kami Kim; Anthony Jaworowski; Terrie Taylor; Wilson Mandala; Karl Seydel; Stephen Rogerson. 2018. "Brain swelling is independent of peripheral plasma cytokine levels in Malawian children with cerebral malaria." Malaria Journal 17, no. 1: 435.

Journal article
Published: 08 February 2018 in Blood
Reads 0
Downloads 0
ACS Style

Stephen Opat; Anna C. Hearps; Kevin Thia; Agnes Yuen; Ben Rogers; Mkunde Chachage; Gregory Moore; Jake Shortt; Georgina Ryland; Piers Blombery; Anthony P. Schwarer; Tahereh Noori; Joseph A. Trapani; Anthony Jaworowski; Ilia Voskoboinik. Adaptive reprogramming of NK cells in X-linked lymphoproliferative syndrome. Blood 2018, 131, 699 -702.

AMA Style

Stephen Opat, Anna C. Hearps, Kevin Thia, Agnes Yuen, Ben Rogers, Mkunde Chachage, Gregory Moore, Jake Shortt, Georgina Ryland, Piers Blombery, Anthony P. Schwarer, Tahereh Noori, Joseph A. Trapani, Anthony Jaworowski, Ilia Voskoboinik. Adaptive reprogramming of NK cells in X-linked lymphoproliferative syndrome. Blood. 2018; 131 (6):699-702.

Chicago/Turabian Style

Stephen Opat; Anna C. Hearps; Kevin Thia; Agnes Yuen; Ben Rogers; Mkunde Chachage; Gregory Moore; Jake Shortt; Georgina Ryland; Piers Blombery; Anthony P. Schwarer; Tahereh Noori; Joseph A. Trapani; Anthony Jaworowski; Ilia Voskoboinik. 2018. "Adaptive reprogramming of NK cells in X-linked lymphoproliferative syndrome." Blood 131, no. 6: 699-702.

Basic science
Published: 13 November 2017 in AIDS
Reads 0
Downloads 0

Objective: The role of high-density lipoprotein (HDL) function in HIV-related atherosclerotic cardiovascular disease (CVD) is unclear. HDLs isolated from HIV+ [HIV(+)HDL] and HIV-uninfected individuals [HIV(–)HDL] were assessed for HDL function and ability to promote monocyte-derived foam cell formation (MDFCF; a key event in HIV-related CVD) ex vivo. Design/methods: Using an established in-vitro model of atherogenesis and plasma samples from an established cross-sectional study of virologically suppressed HIV+ men on stable effective antiretroviral therapy and with low CVD risk (median age: 42 years; n = 10), we explored the impact of native HDL [HIV(+)HDL] on MDFCF. In this exploratory study, we selected HIV(+)HDL known to be dysfunctional based on two independent measures of impaired HDL function: antioxidant (high HDLox) ability of HDL to release apolipoprotein A-I (ApoA-I) (low HDL-ApoA-I exchange). Five healthy men matched by age and race to the HIV+ group were included. Given that oxidation of HDL leads to abnormal HDL function, we also compared proatherogenic effects of HIV(+)HDL vs. chemically derived HDLox. The ex-vivo atherogenesis assay was performed using lipoproteins (purchased or isolated from plasma using ultracentrifugation) and monocytes purified via negative selection from healthy donors. Results: HIV(+)HDL known to have reduced antioxidant function and rate of HDL/ApoAI exchange promoted MDFCF to a greater extent than HDL (33.0 vs. 26.2% foam cells; P = 0.015). HDL oxidized in vitro also enhanced foam cell formation as compared with nonoxidized HDL (P < 0.01). Conclusion: Dysfunctional HDL in virologically suppressed HIV+ individuals may potentiate atherosclerosis in HIV infection by promoting MDFCF. The role of HDL function in HIV-related atherosclerotic CVD is unclear. HDL isolated from HIV+ [HIV(+)HDL] and HIV-uninfected individuals [HIV(−)HDL] were assessed for HDL function and ability to promote foam cell formation ex vivo. HIV(+)HDL known to have reduced antioxidant function and rate of HDL/ApoA1 exchange promoted MDFCF to a greater extent than HDL(−)HDL (33.0 vs. 26.2% foam cells. Subject codes: Inflammation, Lipids and Cholesterol, Vascular Biology, Oxidant Stress, Atherosclerosis

ACS Style

Thomas Angelovich; Anna C. Hearps; Michael N. Oda; Mark S. Borja; Diana Huynh; Stefanie Homann; Anthony Jaworowski; Theodoros Kelesidis. Dysfunctional high-density lipoprotein from HIV+ individuals promotes monocyte-derived foam cell formation in vitro. AIDS 2017, 31, 2331 -2336.

AMA Style

Thomas Angelovich, Anna C. Hearps, Michael N. Oda, Mark S. Borja, Diana Huynh, Stefanie Homann, Anthony Jaworowski, Theodoros Kelesidis. Dysfunctional high-density lipoprotein from HIV+ individuals promotes monocyte-derived foam cell formation in vitro. AIDS. 2017; 31 (17):2331-2336.

Chicago/Turabian Style

Thomas Angelovich; Anna C. Hearps; Michael N. Oda; Mark S. Borja; Diana Huynh; Stefanie Homann; Anthony Jaworowski; Theodoros Kelesidis. 2017. "Dysfunctional high-density lipoprotein from HIV+ individuals promotes monocyte-derived foam cell formation in vitro." AIDS 31, no. 17: 2331-2336.

Video audio media
Published: 17 October 2017 in Journal of Visualized Experiments
Reads 0
Downloads 0

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Atherosclerosis, a leading cause of CAD, is initiated by the transmigration of innate immune monocytes to inflammatory sites of deposited lipid called fatty streaks, which are present in arterial walls of medium to large arteries. The key pathogenic feature of lesions at this early stage of atherosclerosis is the maturation of monocytes which migrate into arteries to form foam cells or lipid-laden macrophages. Considerable evidence supports the hypothesis that risk of atherosclerosis is increased by chronic inflammatory conditions accompanying diseases such as rheumatoid arthritis and HIV, as well as general ageing, and that this risk is predicted by monocyte activation. While mouse models provide a good platform to investigate the role of monocytes in atherogenesis in vivo, they require genetic alteration of natural cholesterol metabolism and drastic alteration of normal mouse diets, and have limited suitability for the study of atherogenic influences of human comorbid diseases. This motivated us to develop a human in vitro model to measure the atherogenic potential of monocytes isolated from individuals with defined disease states. Currently, human in vitro models are limiting in that they evaluate monocyte transmigration and foam cell formation in isolation. Here we describe a protocol in which monocytes isolated from patient blood transmigrate across human endothelial cells into a type 1 collagen matrix, and their propensity to mature into foam cells in the presence or absence of exogenous lipid is measured. The protocol has been validated for the use of human monocytes purified from individuals with HIV infection and elderly HIV uninfected individuals. This model is versatile and allows monocyte transmigration and foam cell formation to be evaluated using either microscopy or flow cytometry as well as allowing the assessment of atherogenic factors present in serum or plasma.

ACS Style

Thomas A. Angelovich; Anna C. Hearps; Anna Maisa; Theodoros Kelesidis; Anthony Jaworowski. Quantification of Monocyte Transmigration and Foam Cell Formation from Individuals with Chronic Inflammatory Conditions. Journal of Visualized Experiments 2017, 1 .

AMA Style

Thomas A. Angelovich, Anna C. Hearps, Anna Maisa, Theodoros Kelesidis, Anthony Jaworowski. Quantification of Monocyte Transmigration and Foam Cell Formation from Individuals with Chronic Inflammatory Conditions. Journal of Visualized Experiments. 2017; (128):1.

Chicago/Turabian Style

Thomas A. Angelovich; Anna C. Hearps; Anna Maisa; Theodoros Kelesidis; Anthony Jaworowski. 2017. "Quantification of Monocyte Transmigration and Foam Cell Formation from Individuals with Chronic Inflammatory Conditions." Journal of Visualized Experiments , no. 128: 1.

Video audio media
Published: 12 October 2017 in Journal of Visualized Experiments
Reads 0
Downloads 0

Low high-density lipoprotein cholesterol (HDL-C) levels are one of the most powerful independent negative predictors of atherosclerotic cardiovascular disease (CVD). The structure and function of HDL rather than HDL-C may more accurately predict atherosclerosis. Several HDL protein and lipid compositional changes that impair HDL function occur in inflammatory states such as atherosclerosis. HDL function is usually determined by cell based assays such as cholesterol efflux assay but these assays have numerous drawbacks lack of standardization. Cell-free assays may give more robust measures of HDL function compared to cell-based assays. HDL oxidation impairs HDL function. HDL has a major role in lipid peroxide transport and high amount of lipid peroxides is related to abnormal HDL function. Lipid-probe interactions should be considered when interpreting the results of non-enzymatic fluorescence assays for measuring the lipid oxidative state. This motivated us to develop a cell-free biochemical enzymatic method to assess HDL lipid peroxide content (HDLox) that contributes to HDL dysfunction. This method is based on the enzyme horseradish peroxidase (HRP) and the fluorochrome Amplex Red that can quantify (without cholesterol oxidase) the lipid peroxide content per mg of HDL-C. Here a protocol is describedfor determination of HDL-lipid peroxidation using the fluorochrome reagent. Assay variability can be reduced by strict standardization of experimental conditions. Higher HDLox values are associated with reduced HDL antioxidant function. The readout of this assay is associated with readouts of validated cell-based assays, surrogate measures of cardiovascular disease, systemic inflammation, immune dysfunction, and associated cardiovascular and metabolic risk phenotypes. This technical approach is a robust method to assess HDL function in human disease where systemic inflammation, oxidative stress and oxidized lipids have a key role (such as atherosclerosis).

ACS Style

Shubhendu Sen Roy; Huy Cong Xuan Nguyen; Thomas Angelovich; Anna C. Hearps; Diana Huynh; Anthony Jaworowski; Theodoros Kelesidis. Cell-free Biochemical Fluorometric Enzymatic Assay for High-throughput Measurement of Lipid Peroxidation in High Density Lipoprotein. Journal of Visualized Experiments 2017, e56325 -e56325.

AMA Style

Shubhendu Sen Roy, Huy Cong Xuan Nguyen, Thomas Angelovich, Anna C. Hearps, Diana Huynh, Anthony Jaworowski, Theodoros Kelesidis. Cell-free Biochemical Fluorometric Enzymatic Assay for High-throughput Measurement of Lipid Peroxidation in High Density Lipoprotein. Journal of Visualized Experiments. 2017; (128):e56325-e56325.

Chicago/Turabian Style

Shubhendu Sen Roy; Huy Cong Xuan Nguyen; Thomas Angelovich; Anna C. Hearps; Diana Huynh; Anthony Jaworowski; Theodoros Kelesidis. 2017. "Cell-free Biochemical Fluorometric Enzymatic Assay for High-throughput Measurement of Lipid Peroxidation in High Density Lipoprotein." Journal of Visualized Experiments , no. 128: e56325-e56325.

Journal article
Published: 19 September 2017 in Journal of Leukocyte Biology
Reads 0
Downloads 0

Influenza epidemics lead to severe illness, life-threatening complications, and deaths, especially in the elderly. As CD8+ T cells are associated with rapid recovery from influenza, we investigated the effects of aging on antigen-specific CD8+ T cells across the universal influenza epitopes in humans. We show that aging is characterized by altered frequencies in T cell subsets, with naive T cells being partially replaced by activated effector/memory populations. Although we observed no striking differences in TCR signaling capacity, T cells in the elderly had increased expression of transcription factors Eomes and T-bet, and such changes were most apparent in CD8+ T cells. Strikingly, the numbers of antigen-specific CD8+ T cells across universal influenza epitopes were reduced in the elderly, although their effector/memory phenotypes remained stable. To understand whether diminished numbers of influenza-specific CD8+ T cells in the elderly resulted from alteration in TCR clonotypes, we dissected the TCRαβ repertoire specific for the prominent HLA-A*02:01-restricted-M158–66 (A2/M158) influenza epitope. We provide the first ex vivo data on paired antigen-specific TCRαβ clonotypes in the elderly, showing that influenza-specific A2/M158+ TCRαβ repertoires in the elderly adults varied from those in younger adults, with the main features being a reduction in the frequency of the public TRAV27–TRBV19 TCRαβ clonotype, increased proportion of private TCRαβ signatures, broader use of TRAV and TRBV gene segments, and large clonal expansion of private TCRαβ clonotypes with longer CDR3 loops. Our study supports the development of T cell-targeted influenza vaccines that would boost the T cell compartment during life and maintain the numbers and optimal TCRαβ signatures in the elderly.

ACS Style

Thi H. O. Nguyen; Sneha Sant; Nicola L. Bird; Emma J. Grant; E. Bridie Clemens; Marios Koutsakos; Sophie A. Valkenburg; Stephanie Gras; Martha Lappas; Anthony Jaworowski; Jane Crowe; Liyen Loh; Katherine Kedzierska. Perturbed CD8 + T cell immunity across universal influenza epitopes in the elderly. Journal of Leukocyte Biology 2017, 1 -207R.

AMA Style

Thi H. O. Nguyen, Sneha Sant, Nicola L. Bird, Emma J. Grant, E. Bridie Clemens, Marios Koutsakos, Sophie A. Valkenburg, Stephanie Gras, Martha Lappas, Anthony Jaworowski, Jane Crowe, Liyen Loh, Katherine Kedzierska. Perturbed CD8 + T cell immunity across universal influenza epitopes in the elderly. Journal of Leukocyte Biology. 2017; ():1-207R.

Chicago/Turabian Style

Thi H. O. Nguyen; Sneha Sant; Nicola L. Bird; Emma J. Grant; E. Bridie Clemens; Marios Koutsakos; Sophie A. Valkenburg; Stephanie Gras; Martha Lappas; Anthony Jaworowski; Jane Crowe; Liyen Loh; Katherine Kedzierska. 2017. "Perturbed CD8 + T cell immunity across universal influenza epitopes in the elderly." Journal of Leukocyte Biology , no. : 1-207R.

Original research article
Published: 30 June 2017 in Frontiers in Immunology
Reads 0
Downloads 0

Innate immune dysfunction persists in HIV+ individuals despite effective combination antiretroviral therapy (cART). We recently demonstrated that an adaptive-like CD56dim NK cell population lacking the signal transducing protein FcRγ is expanded in HIV+ individuals. Here we analysed a cohort of HIV+ men who have sex with men (MSM, n=20) at baseline and following 6, 12 and 24 months of cART, and compared them with uninfected MSM (n=15) to investigate the impact of cART on NK cell dysfunction. Proportions of NK cells expressing markers of early (HLA-DR+/CD38+ and CD69+) and late (HLA-DR+/CD38+) activation ed NK cells were elevated in cART-naïve HIV+ MSM (p=0.004 and 0.015 and 0.004, respectively), as were adaptive FcRγ- NK cells (p=0.003). Using latent growth curve modelling, we show that cART did not reduce levels of adaptive FcRγ- NK cells (p=0.115) or activated HLA-DR+/CD38+ NK cells (p=0.129) but did reduce T cell and monocyte activation (p<0.001 for all). Proportions of adaptive FcRγ- NK cells were not associated with NK cell, T cell or monocyte activation, suggesting different factors drive CD56dim FcRγ- adaptive NK cell expansion and immune activation in HIV+ individuals. Whilst proportions of activated CD69+ NK cells declined significantly on cART (p=0.003), the rate was significantly slower than the decline of T cell and monocyte activation, indicating a reduced potency of cART against NK cell activation. Our findings indicate that two years of suppressive cART have no impact on adaptive CD56dim FcRγ- NK cell expansion and that NK cell activation persists after normalisation of other immune parameters. This may have implications for the development of malignancies and co-morbidities in HIV+ individuals on cART.

ACS Style

Anna C. Hearps; Paul Agius; Jingling Zhou; Samantha Brunt; Mkunde Chachage; Thomas A. Angelovich; Paul U. Cameron; Michelle Giles; Patricia Price; Julian Elliott; Anthony Jaworowski. Persistence of Activated and Adaptive-Like NK Cells in HIV+ Individuals despite 2 Years of Suppressive Combination Antiretroviral Therapy. Frontiers in Immunology 2017, 8, 1 .

AMA Style

Anna C. Hearps, Paul Agius, Jingling Zhou, Samantha Brunt, Mkunde Chachage, Thomas A. Angelovich, Paul U. Cameron, Michelle Giles, Patricia Price, Julian Elliott, Anthony Jaworowski. Persistence of Activated and Adaptive-Like NK Cells in HIV+ Individuals despite 2 Years of Suppressive Combination Antiretroviral Therapy. Frontiers in Immunology. 2017; 8 ():1.

Chicago/Turabian Style

Anna C. Hearps; Paul Agius; Jingling Zhou; Samantha Brunt; Mkunde Chachage; Thomas A. Angelovich; Paul U. Cameron; Michelle Giles; Patricia Price; Julian Elliott; Anthony Jaworowski. 2017. "Persistence of Activated and Adaptive-Like NK Cells in HIV+ Individuals despite 2 Years of Suppressive Combination Antiretroviral Therapy." Frontiers in Immunology 8, no. : 1.

Journal article
Published: 10 April 2017 in Journal of Periodontal Research
Reads 0
Downloads 0

Background and ObjectivePeriodontal disease has been associated with cardiovascular disease in the general population. It is unknown whether IgG antibody levels for periodontal pathogens are associated with the diagnosis of coronary artery disease (CAD) in HIV-positive individuals.Material and MethodsTwenty-four HIV-positive individuals (cases) with stored plasma available in the 12 months before CAD diagnosis were age- and sex-matched 1:2 with 46 HIV-positive individuals without CAD (controls). Antibody levels to whole cell extracts from periodontal pathogens Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum, as well as markers of inflammation sCD14, CXCL10 and high-sensitivity C-reactive protein, were compared between cases and controls using enzyme-linked immunosorbent assays.ResultsP. gingivalis-specific IgG levels (μg/mL) were significantly higher in individuals with CAD (median 1.48 [IQR 1.06-2.05]) compared to controls (0.70 [IQR 0.35-1.24], P<.001), and remained significantly higher following adjustment for traditional cardiovascular risk factors and HIV viral load (OR 21.6 [95% CI 3.73-125.63] P=.001). There was a borderline association between A. actinomycetemcomitans IgG antibody levels (cases, median 3.86 [IQR 3.19-4.72]; controls, 3.34 [IQR 2.59-4.07], P=.050) and no association found between F. nucleatum antibody levels and CAD. sCD14 levels (μg/mL) were higher in cases compared with controls (median 3.45 [IQR 3.03-4.11] vs 2.65 [IQR 2.32-2.99] P<.001), while CXCL10 (median 127 pg/mL [IQR 88-157] vs 153 [IQR 90-244] P=.321) and high-sensitivity C-reactive protein (median 3.44 mg/L [1.98-5.32] vs 1.85 [1.13-6.88] P=.203) levels were not different between cases and controls.ConclusionPeriodontal bacteria may be contributing to CAD risk in HIV-positive individuals.

ACS Style

V. L. Berquist; A. C. Hearps; P. Ford; Anthony Jaworowski; S. J. Leishman; J. F. Hoy; Janine Trevillyan. Porphyromonas gingivalis antibody levels and diagnosis of coronary artery disease in HIV-positive individuals. Journal of Periodontal Research 2017, 52, 930 -935.

AMA Style

V. L. Berquist, A. C. Hearps, P. Ford, Anthony Jaworowski, S. J. Leishman, J. F. Hoy, Janine Trevillyan. Porphyromonas gingivalis antibody levels and diagnosis of coronary artery disease in HIV-positive individuals. Journal of Periodontal Research. 2017; 52 (5):930-935.

Chicago/Turabian Style

V. L. Berquist; A. C. Hearps; P. Ford; Anthony Jaworowski; S. J. Leishman; J. F. Hoy; Janine Trevillyan. 2017. "Porphyromonas gingivalis antibody levels and diagnosis of coronary artery disease in HIV-positive individuals." Journal of Periodontal Research 52, no. 5: 930-935.