Natasa Strbo

Dr. Natasa Strbo

orcid

Research Focus & Metrics

Academic Career Length

14Years (2013-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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16 September 2020 in Frontiers in Immunology
Verified
Journal Article
Open access
PDF file
IPIrena Pastar
Irena Pastar
KOKatelyn O’nEill
Katelyn O’nEill
LPLaura Padula
Laura Padula
CHCheyanne R. Head
Cheyanne R. Head
JBJamie L. Burgess
Jamie L. Burgess
NSNatasa Strbo
Natasa Strbo
Perforin-2 (P-2) is an antimicrobial protein with unique properties to kill intracellular bacteria. Gamma delta (GD) T cells, as the major T cell population in epithelial tissues, play a central role in protective and pathogenic immune responses in the skin. However, the tissue-specific mechanisms that control the innate immune response and the effector functions of GD T cells, especially the cross-talk with commensal organisms, are not very well understood. We hypothesized that the most prevalent skin commensal microorganism,Staphylococcus epidermidis, may play a role in regulating GD T cell-mediated cutaneous responses. We analyzed antimicrobial protein P-2 expression in human skin at a single cell resolution using an amplified fluorescencein situhybridization approach to detect P-2 mRNA in combination with immunophenotyping. We show thatS. epidermidisactivates GD T cells and upregulates P-2 in human skinex vivoin a cell-specific manner. Furthermore, P-2 upregulation followingS. epidermidisstimulation correlates with increased ability of skin cells to kill intracellularStaphylococcus aureus. Our findings are the first to reveal that skin commensal bacteria induce P-2 expression, which may be utilized beneficially to modulate host innate immune responses and protect from skin infections.

15 December 2021 in Journal of Clinical Investigation
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Journal Article
Closed access
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IPIrena Pastar
Irena Pastar
ASAndrew P. Sawaya
Andrew P. Sawaya
JMJelena Marjanovic
Jelena Marjanovic
JBJamie Burgess
Jamie Burgess
NSNatasa Strbo
Natasa Strbo
MTMarjana Tomic-Canic
Marjana Tomic-Canic
Impaired wound healing associated with recurrent Staphylococcus aureus infection and unresolved inflammation are hallmarks of nonhealing diabetic foot ulcers (DFUs). Perforin-2, an innate immunity molecule against intracellular bacteria, limits cutaneous infection and dissemination of S. aureus in mice. Here, we report the intracellular accumulation of S. aureus in the epidermis of DFUs with no clinical signs of infection due to marked suppression of perforin-2. S. aureus residing within the epidermis of DFUs triggers AIM2 inflammasome activation and pyroptosis. These findings were corroborated in mice lacking perforin-2. The effects of pyroptosis on DFU clinical outcomes were further elucidated in a 4-week longitudinal clinical study in patients with DFUs receiving standard care. Increased AIM2 inflammasome and ASC-pyroptosome coupled with induction of IL-1β were found in nonhealing DFUs compared with healing DFUs. Our findings revealed that perforin-2 suppression, intracellular S. aureus accumulation, and associated induction of pyroptosis contribute to healing inhibition and prolonged inflammation in patients with DFUs.

20 November 2013 in Immunologic Research
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Journal Article
Closed access
PDF file
NSNatasa Strbo
Natasa Strbo
AGArlene Garcia-Soto
Arlene Garcia-Soto
TSTaylor H. Schreiber
Taylor H. Schreiber
EPEckhard R. Podack
Eckhard R. Podack

4 January 2019 in Experimental Dermatology
Verified
Journal Article
Closed access
PDF file
NSNatasa Strbo
Natasa Strbo
IPIrena Pastar
Irena Pastar
LRLaura Romero
Laura Romero
VCVivien Chen
Vivien Chen
MVMilos Vujanac
Milos Vujanac
MTMarjana Tomic-Canic
Marjana Tomic-Canic

14 August 2020 in Frontiers in Immunology
Verified
Journal Article
Open access
PDF file
KOKatelyn O'Neill
Katelyn O'Neill
IPIrena Pastar
Irena Pastar
MTMarjana Tomic-Canic
Marjana Tomic-Canic
NSNatasa Strbo
Natasa Strbo
Gamma delta (GD) T cells are an unconventional T cell type present in both the epidermis and the dermis of human skin. They are critical to regulating skin inflammation, wound healing, and anti-microbial defense. Similar to CD8+ cytotoxic T cells expressing an alpha beta (AB) TCR, GD T cells have cytolytic capabilities. They play an important role in elimination of cutaneous tumors and virally infected cells and have also been implicated in pathogenicity of several autoimmune diseases. T cell cytotoxicity is associated with the expression of the pore forming protein Perforin. Perforin is an innate immune protein containing a membrane attack complex perforin-like (MACPF) domain and functions by forming pores in the membranes of target cells, which allow granzymes and reactive oxygen species to enter the cells and destroy them. Perforin-2, encoded by the gene MPEG1, is a newly discovered member of this protein family that is critical for clearance of intracellular bacteria. Cutaneous GD T cells express both Perforin and Perforin-2, but many questions remain regarding the role that these proteins play in GD T cell mediated cytotoxicity against tumors and bacterial pathogens. Here, we review what is known about Perforin expression by skin GD T cells and the mechanisms that contribute to Perforin activation.

15 December 2015 in American Journal of Reproductive Immunology
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Journal Article
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NSNatasa Strbo
Natasa Strbo
MAMaria L. Alcaide
Maria L. Alcaide
LRLaura Romero
Laura Romero
HBHector Bolivar
Hector Bolivar
DJDeborah Jones
Deborah Jones
MFMargaret A. Fischl
Margaret A. Fischl