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Dr. Charles BODET
Laboratory of Inflammation, Epithelial Tissues and Cytokines, LITEC EA-4331, University of Poitiers, Poitiers, France

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0 Cell Signaling
0 Innate Immunity
0 skin inflammation
0 Microbial pathogenesis
0 Antimicrobial compounds

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Article
Published: 17 August 2021
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Usutu virus (USUV) and West Nile virus (WNV) are emerging flaviviruses transmitted by mosquitoes. Although they differ in their endemicity, with WNV present throughout much of the world and USUV currently limited to Africa and Europe, both constitute a global public health threat. Since they are directly inoculated in the epidermis and the dermis during mosquito bites, the skin constitutes the initial site of viral replication and immune response. The skin is equipped with a unique network of dendritic cells, which represent an essential outpost of immune defenses. These skin-resident DCs comprise Langerhans cells (LCs) in the epidermis and dermal DCs in the dermis, which capture pathogens through the C-type lectin receptors (CLR) langerin and DC-SIGN, respectively. Despite the key role of these cells in the body’s antiviral defenses, their implication in the immune control and replication of WNV and USUV is not known. Using human skin explants, we show that while both viruses can replicate in keratinocytes, they can also infect resident DCs with distinct tropism, since WNV preferentially infects DCs in the dermis, whereas USUV has a greater propensity to infect LCs. Using both purified human epidermal LCs (eLCs) and monocyte derived LCs (MoLCs), we confirm that LCs sustain a faster and more efficient replication of USUV compared with WNV and that this correlates with a more intense innate immune response to USUV compared with WNV. Next, we show that ectopic expression of langerin in non-permissive cells rendered them permissive to USUV, but not to WNV. Conversely, blocking or silencing langerin in MoLCs or eLCs made them resistant to USUV infection, thus demonstrating that this specific CLR allows USUV to enter and productively infect LCs. Altogether, our results demonstrate that LCs constitute privileged target cells for USUV in human skin, because langerin favors its entry and replication. Intriguingly, this suggests that USUV efficiently escapes the antiviral functions of langerin, which normally safeguards LCs from most viral infections.

ACS Style

Marie-France Martin; Ghizlane Maarifi; Hervé Abiven; Marine Seffals; Nicolas Mouchet; Cécile Beck; Charles Bodet; Nicolas Lévèque; Nathalie J. Arhel; Fabien P. Blanchet; Yannick Simonin; Sébastien Nisole. Usutu virus uses langerin as a receptor to productively infect Langerhans cells more efficiently than West Nile virus. 2021, 1 .

AMA Style

Marie-France Martin, Ghizlane Maarifi, Hervé Abiven, Marine Seffals, Nicolas Mouchet, Cécile Beck, Charles Bodet, Nicolas Lévèque, Nathalie J. Arhel, Fabien P. Blanchet, Yannick Simonin, Sébastien Nisole. Usutu virus uses langerin as a receptor to productively infect Langerhans cells more efficiently than West Nile virus. . 2021; ():1.

Chicago/Turabian Style

Marie-France Martin; Ghizlane Maarifi; Hervé Abiven; Marine Seffals; Nicolas Mouchet; Cécile Beck; Charles Bodet; Nicolas Lévèque; Nathalie J. Arhel; Fabien P. Blanchet; Yannick Simonin; Sébastien Nisole. 2021. "Usutu virus uses langerin as a receptor to productively infect Langerhans cells more efficiently than West Nile virus." , no. : 1.

Journal article
Published: 24 July 2021 in Pharmaceuticals
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Hg-CATH and Pb-CATH4 are cathelicidins from Heterocephalus glaber and Python bivittatus that have been previously identified as potent antibacterial peptides. However, their antiviral properties were not previously investigated. In this study, their activity against the herpes simplex virus (HSV)-1 was evaluated during primary human keratinocyte infection. Both of them significantly reduced HSV-1 DNA replication and production of infectious viral particles in keratinocytes at noncytotoxic concentrations, with the stronger activity of Pb-CATH4. These peptides did not show direct virucidal activity and did not exhibit significant immunomodulatory properties, except for Pb-CATH4, which exerted a moderate proinflammatory action. All in all, our results suggest that Hg-CATH and Pb-CATH4 could be potent candidates for the development of new therapies against HSV-1.

ACS Style

Alexia Damour; Magali Garcia; Hye-Sun Cho; Andy Larivière; Nicolas Lévêque; Chankyu Park; Charles Bodet. Characterisation of Antiviral Activity of Cathelicidins from Naked Mole Rat and Python bivittatus on Human Herpes Simplex Virus 1. Pharmaceuticals 2021, 14, 715 .

AMA Style

Alexia Damour, Magali Garcia, Hye-Sun Cho, Andy Larivière, Nicolas Lévêque, Chankyu Park, Charles Bodet. Characterisation of Antiviral Activity of Cathelicidins from Naked Mole Rat and Python bivittatus on Human Herpes Simplex Virus 1. Pharmaceuticals. 2021; 14 (8):715.

Chicago/Turabian Style

Alexia Damour; Magali Garcia; Hye-Sun Cho; Andy Larivière; Nicolas Lévêque; Chankyu Park; Charles Bodet. 2021. "Characterisation of Antiviral Activity of Cathelicidins from Naked Mole Rat and Python bivittatus on Human Herpes Simplex Virus 1." Pharmaceuticals 14, no. 8: 715.

Review
Published: 30 March 2021 in Viruses
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The poly-adenosine diphosphate (ADP)-ribose polymerases (PARPs) are responsible for ADP-ribosylation, a reversible post-translational modification involved in many cellular processes including DNA damage repair, chromatin remodeling, regulation of translation and cell death. In addition to these physiological functions, recent studies have highlighted the role of PARPs in host defenses against viruses, either by direct antiviral activity, targeting certain steps of virus replication cycle, or indirect antiviral activity, via modulation of the innate immune response. This review focuses on the antiviral activity of PARPs, as well as strategies developed by viruses to escape their action.

ACS Style

Mathilde Malgras; Magali Garcia; Clément Jousselin; Charles Bodet; Nicolas Lévêque. The Antiviral Activities of Poly-ADP-Ribose Polymerases. Viruses 2021, 13, 582 .

AMA Style

Mathilde Malgras, Magali Garcia, Clément Jousselin, Charles Bodet, Nicolas Lévêque. The Antiviral Activities of Poly-ADP-Ribose Polymerases. Viruses. 2021; 13 (4):582.

Chicago/Turabian Style

Mathilde Malgras; Magali Garcia; Clément Jousselin; Charles Bodet; Nicolas Lévêque. 2021. "The Antiviral Activities of Poly-ADP-Ribose Polymerases." Viruses 13, no. 4: 582.

Journal article
Published: 31 August 2020 in Journal of Clinical Medicine
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This study aims to determine the gastric distribution, density, and diversity of Helicobacter pylori infection. Subtotal resection of the stomachs of three H. pylori-infected and asymptomatic obese patients were collected after a sleeve gastrectomy. Distribution and density of H. pylori were determined using culture and RT-PCR on multiple gastric sites (88, 176, and 101 biopsies per patient). Diversity of H. pylori strains was studied using antibiotic susceptibility testing, random amplified polymorphism DNA (RAPD) typing and cagA gene detection on single-colony isolates (44, 96, and 49 isolates per patient). H. pylori was detected in nearly all analyzed sites (354/365 biopsies, 97%). Antral density was higher in one patient only. The three stomachs were almost exclusively infected by an antibiotic-susceptible strain. One clarithromycin-resistant isolate in one biopsy was detected in two stomachs (1/44 and 1/49 isolates), while in the third one, eight (8/96 isolates) metronidazole-resistant isolates were detected. DNA typing showed infection with cagA-negative strains for one patient, cagA-positive strains for a second patient and the third patient was infected with two different strains of distinct cagA genotypes. Infection with H. pylori is shown to spread to the whole surface of the stomach, but a possibility of minor sub-population of antibiotic-resistant clones, undetectable in routine practice.

ACS Style

Maxime Pichon; Cong Tri Tran; Gaëtan Motillon; Charlotte Debiais; Sylvain Gautier; Marie Aballea; Julie Cremniter; Philippe Vasseur; David Tougeron; Magali Garcia; Martine Garnier; Charles Bodet; Jean Pierre Faure; Christophe Burucoa. Where to Biopsy to Detect Helicobacter pylori and How Many Biopsies Are Needed to Detect Antibiotic Resistance in a Human Stomach. Journal of Clinical Medicine 2020, 9, 2812 .

AMA Style

Maxime Pichon, Cong Tri Tran, Gaëtan Motillon, Charlotte Debiais, Sylvain Gautier, Marie Aballea, Julie Cremniter, Philippe Vasseur, David Tougeron, Magali Garcia, Martine Garnier, Charles Bodet, Jean Pierre Faure, Christophe Burucoa. Where to Biopsy to Detect Helicobacter pylori and How Many Biopsies Are Needed to Detect Antibiotic Resistance in a Human Stomach. Journal of Clinical Medicine. 2020; 9 (9):2812.

Chicago/Turabian Style

Maxime Pichon; Cong Tri Tran; Gaëtan Motillon; Charlotte Debiais; Sylvain Gautier; Marie Aballea; Julie Cremniter; Philippe Vasseur; David Tougeron; Magali Garcia; Martine Garnier; Charles Bodet; Jean Pierre Faure; Christophe Burucoa. 2020. "Where to Biopsy to Detect Helicobacter pylori and How Many Biopsies Are Needed to Detect Antibiotic Resistance in a Human Stomach." Journal of Clinical Medicine 9, no. 9: 2812.

Review article
Published: 03 June 2020 in Frontiers in Microbiology
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Keratinocytes, the main cells of the epidermis, are the first site of replication as well as the first line of defense against many viruses such as arboviruses, enteroviruses, herpes viruses, human papillomaviruses, or vaccinia virus. During viral replication, these cells can sense virus associated molecular patterns leading to the initiation of an innate immune response composed of pro-inflammatory cytokines, chemokines, and antimicrobial peptides. Human keratinocytes produce and secrete at least nine antimicrobial peptides: human cathelicidin LL-37, types 1–4 human β-defensins, S100 peptides such as psoriasin (S100A7), calprotectin (S100A8/9) and koebnerisin (S100A15), and RNase 7. These peptides can exert direct antiviral effects on the viral particle or its replication cycle, and indirect antiviral activity, by modulating the host immune response. The purpose of this review is to summarize current knowledge of antiviral and immunomodulatory properties of human keratinocyte antimicrobial peptides.

ACS Style

Céline Chessa; Charles Bodet; Clément Jousselin; Michel Wehbe; Nicolas Lévêque; Magali Garcia. Antiviral and Immunomodulatory Properties of Antimicrobial Peptides Produced by Human Keratinocytes. Frontiers in Microbiology 2020, 11, 1155 .

AMA Style

Céline Chessa, Charles Bodet, Clément Jousselin, Michel Wehbe, Nicolas Lévêque, Magali Garcia. Antiviral and Immunomodulatory Properties of Antimicrobial Peptides Produced by Human Keratinocytes. Frontiers in Microbiology. 2020; 11 ():1155.

Chicago/Turabian Style

Céline Chessa; Charles Bodet; Clément Jousselin; Michel Wehbe; Nicolas Lévêque; Magali Garcia. 2020. "Antiviral and Immunomodulatory Properties of Antimicrobial Peptides Produced by Human Keratinocytes." Frontiers in Microbiology 11, no. : 1155.

Journal article
Published: 03 March 2020 in Frontiers in Immunology
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This study aimed to characterize cathelicidins from the gray short-tailed opossum in silico and experimentally validate their antimicrobial effects against various pathogenic bacteria and West Nile virus (WNV). Genome-wide in silico analysis against the current genome assembly of the gray short-tailed opossum yielded 56 classical antimicrobial peptides (AMPs) from eight different families, among which 19 cathelicidins, namely ModoCath1 – 19, were analyzed in silico to predict their antimicrobial domains and three of which, ModoCath1, -5, and -6, were further experimentally evaluated for their antimicrobial activity, and were found to exhibit a wide spectrum of antimicroial effects against a panel of gram-positive and gram-negative bacterial strains. In addition, these peptides displayed low-to-moderate cytotoxicity in mammalian cells as well as stability in serum and various salt and pH conditions. Circular dichroism analysis of the spectra resulting from interactions between ModoCaths and lipopolysaccharides (LPS) showed formation of a helical structure, while a dual-dye membrane disruption assay and scanning electron microscopy analysis revealed that ModoCaths exerted bactericidal effects by causing membrane damage. Furthermore, ModoCath5 displayed potent antiviral activity against WNV by inhibiting viral replication, suggesting that opossum cathelicidins may serve as potentially novel antimicrobial endogenous substances of mammalian origin, considering their large number. Moreover, analysis of publicly available RNA-seq data revealed the expression of eight ModoCaths from five different tissues, suggesting that gray short-tailed opossums may be an interesting source of cathelicidins with diverse characteristics.

ACS Style

Hye-Sun Cho; Joori Yum; Andy Larivière; Nicolas Lévêque; Quy Van Chanh Le; Byeongyong Ahn; Hyoim Jeon; Kwonho Hong; Nagasundarapandian Soundrarajan; Jin-Hoi Kim; Charles Bodet; Chankyu Park. Opossum Cathelicidins Exhibit Antimicrobial Activity Against a Broad Spectrum of Pathogens Including West Nile Virus. Frontiers in Immunology 2020, 11, 347 .

AMA Style

Hye-Sun Cho, Joori Yum, Andy Larivière, Nicolas Lévêque, Quy Van Chanh Le, Byeongyong Ahn, Hyoim Jeon, Kwonho Hong, Nagasundarapandian Soundrarajan, Jin-Hoi Kim, Charles Bodet, Chankyu Park. Opossum Cathelicidins Exhibit Antimicrobial Activity Against a Broad Spectrum of Pathogens Including West Nile Virus. Frontiers in Immunology. 2020; 11 ():347.

Chicago/Turabian Style

Hye-Sun Cho; Joori Yum; Andy Larivière; Nicolas Lévêque; Quy Van Chanh Le; Byeongyong Ahn; Hyoim Jeon; Kwonho Hong; Nagasundarapandian Soundrarajan; Jin-Hoi Kim; Charles Bodet; Chankyu Park. 2020. "Opossum Cathelicidins Exhibit Antimicrobial Activity Against a Broad Spectrum of Pathogens Including West Nile Virus." Frontiers in Immunology 11, no. : 347.

Review
Published: 13 December 2019 in Clinical Reviews in Allergy & Immunology
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Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in the world. AD is a complex pathology mainly characterized by an impaired skin barrier, immune response dysfunction, and unbalanced skin microbiota. Moreover, AD patients exhibit an increased risk of developing bacterial and viral infections. One of the most current, and potentially life-threatening, viral infection is caused by herpes simplex virus (HSV), which occurs in about 3% of AD patients under the name of eczema herpeticum (EH). Following a first part dedicated to the clinical features, virological diagnosis, and current treatments of EH, this review will focus on the description of the pathophysiology and, more particularly, the presently known predisposing factors to herpetic complications in AD patients. These factors include those related to impairment of the skin barrier such as deficit in filaggrin and anomalies in tight and adherens junctions. In addition, low production of the antimicrobial peptides cathelicidin LL-37 and human β-defensins; overexpression of cytokines such as interleukin (IL)-4, IL-13, IL-25, IL-33, and thymic stromal lymphopoietin (TSLP); or downregulation of type I to III interferons as well as defect in functions of immune cells such as dendritic, natural killer, and regulatory T cells have been involved. Otherwise, genetic polymorphisms and AD topical calcineurin inhibitor treatments have been associated with an increased risk of EH. Finally, dysbiosis of skin microbiota characterized in AD patients by Staphylococcus aureus colonization and toxin secretion, such as α-toxin, has been described as promoting HSV replication and could therefore contribute to EH.

ACS Style

Alexia Damour; Magali Garcia; Julien Seneschal; Nicolas Lévêque; Charles Bodet. Eczema Herpeticum: Clinical and Pathophysiological Aspects. Clinical Reviews in Allergy & Immunology 2019, 59, 1 -18.

AMA Style

Alexia Damour, Magali Garcia, Julien Seneschal, Nicolas Lévêque, Charles Bodet. Eczema Herpeticum: Clinical and Pathophysiological Aspects. Clinical Reviews in Allergy & Immunology. 2019; 59 (1):1-18.

Chicago/Turabian Style

Alexia Damour; Magali Garcia; Julien Seneschal; Nicolas Lévêque; Charles Bodet. 2019. "Eczema Herpeticum: Clinical and Pathophysiological Aspects." Clinical Reviews in Allergy & Immunology 59, no. 1: 1-18.

Journal article
Published: 14 February 2019 in Scientific Reports
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Wound healing is a complex physiological process that repairs a skin lesion and produces fibrous tissue. In some cases, this process can lead to hypertrophic scars (HS) or keloid scars (KS), for which the pathophysiology remains poorly understood. Previous studies have reported the presence of oncostatin M (OSM) during the wound healing process; however, the role of OSM in pathological scarring remains to be precisely elucidated. This study aims to analyse the presence and involvement of OSM in the pathological scarring process. It was conducted with 18 patients, including 9 patients with hypertrophic scarring and 9 patients with keloid scarring. Histological tissue analysis of HS and KS showed minor differences in the organization of the extracellular matrix, the inflammatory infiltrate and the keratinocyte phenotype. Transcriptomic analysis showed increased expression levels of fibronectin, collagen I, TGFβ1, β-defensin-2 and S100A7 in both pathological samples. OSM expression levels were greater in HS than in KS and control skin. In vitro, OSM inhibited TGFβ1-induced secretion of components of the extracellular matrix by normal and pathological fibroblasts. Overall, we suggest that OSM is involved in pathological wound healing processes by inhibiting the evolution of HS towards KS by controlling the fibrotic effect of TGFβ1.

ACS Style

Vincent Huguier; Jean-Philippe Giot; Marie Simonneau; Pierre Levillain; Sandrine Charreau; Martine Garcia; Jean-François Jégou; Charles Bodet; Franck Morel; Jean-Claude Lecron; Laure Favot. Oncostatin M exerts a protective effect against excessive scarring by counteracting the inductive effect of TGFβ1 on fibrosis markers. Scientific Reports 2019, 9, 1 -10.

AMA Style

Vincent Huguier, Jean-Philippe Giot, Marie Simonneau, Pierre Levillain, Sandrine Charreau, Martine Garcia, Jean-François Jégou, Charles Bodet, Franck Morel, Jean-Claude Lecron, Laure Favot. Oncostatin M exerts a protective effect against excessive scarring by counteracting the inductive effect of TGFβ1 on fibrosis markers. Scientific Reports. 2019; 9 (1):1-10.

Chicago/Turabian Style

Vincent Huguier; Jean-Philippe Giot; Marie Simonneau; Pierre Levillain; Sandrine Charreau; Martine Garcia; Jean-François Jégou; Charles Bodet; Franck Morel; Jean-Claude Lecron; Laure Favot. 2019. "Oncostatin M exerts a protective effect against excessive scarring by counteracting the inductive effect of TGFβ1 on fibrosis markers." Scientific Reports 9, no. 1: 1-10.

Communication
Published: 18 January 2019 in Viruses
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Temporins are anti-microbial peptides synthesized in the skin of frogs of the Ranidae family. The few studies to date that have examined their anti-viral properties have shown that they have potential as anti-viral therapies. In this work, we evaluated the anti-herpes simplex virus type 1 (HSV-1) activity of the temporin-SHa (SHa) and its synthetic analog [K3]SHa. Human cathelicidin LL-37 and temporin-Tb (Tb), previously demonstrated to have anti-HSV-1 properties, were used as positive controls. We observed that SHa and [K3]SHa significantly inhibit HSV-1 replication in human primary keratinocytes when used at micromolar concentrations. This anti-viral activity was equivalent to that of Tb, but lower than that of LL-37. Transcriptomic analyses revealed that SHa did not act through the modulation of the cell innate immune response, but rather, displayed virucidal properties by reducing infectious titer of HSV-1 in suspension. In contrast, pre-incubation of the virus with LL-37 suggests that this peptide does not act directly on the viral particle at non-cytotoxic concentrations tested. The anti-HSV-1 activity of LL-37 appears to be due to the potentiation of cellular anti-viral defenses through the induction of interferon stimulated gene expression in infected primary keratinocytes. This study demonstrated that SHa and [K3]SHa, in addition to their previously reported antibacterial and antiparasitic activities, are direct-acting anti-HSV-1 peptides. Importantly, this study extends the little studied anti-viral attributes of frog temporins and offers perspectives for the development of new anti-HSV-1 therapies.

ACS Style

Maëva Roy; Lucie Lebeau; Céline Chessa; Alexia Damour; Ali Ladram; Bruno Oury; David Boutolleau; Charles Bodet; Nicolas Lévêque. Comparison of Anti-Viral Activity of Frog Skin Anti-Microbial Peptides Temporin-Sha and [K3]SHa to LL-37 and Temporin-Tb against Herpes Simplex Virus Type 1. Viruses 2019, 11, 77 .

AMA Style

Maëva Roy, Lucie Lebeau, Céline Chessa, Alexia Damour, Ali Ladram, Bruno Oury, David Boutolleau, Charles Bodet, Nicolas Lévêque. Comparison of Anti-Viral Activity of Frog Skin Anti-Microbial Peptides Temporin-Sha and [K3]SHa to LL-37 and Temporin-Tb against Herpes Simplex Virus Type 1. Viruses. 2019; 11 (1):77.

Chicago/Turabian Style

Maëva Roy; Lucie Lebeau; Céline Chessa; Alexia Damour; Ali Ladram; Bruno Oury; David Boutolleau; Charles Bodet; Nicolas Lévêque. 2019. "Comparison of Anti-Viral Activity of Frog Skin Anti-Microbial Peptides Temporin-Sha and [K3]SHa to LL-37 and Temporin-Tb against Herpes Simplex Virus Type 1." Viruses 11, no. 1: 77.

Original research article
Published: 02 November 2018 in Frontiers in Cellular and Infection Microbiology
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West Nile Virus (WNV) is a flavivirus involved in many human infections worldwide. This arthropod-borne virus is directly co-inoculated with mosquito saliva through the epidermis and the dermis during blood meal. WNV starts replicating in the skin before migrating to the draining lymph node, leading to widespread viremia and in some cases to neurological symptoms. Skin is a complex organ composed of different cell types that together perform essential functions such as pathogen sensing, barrier maintenance and immunity. Keratinocytes, which represent 90% of the cells of the epidermis, are the organism's first line of defense, initiating innate immune response by recognizing pathogens through their pattern recognition receptors. Although WNV was previously known to replicate in human primary keratinocytes, the induced inflammatory response remains unknown. The aim of this study was first to characterize the inflammatory response of human primary keratinocytes to WNV infection and then, to assess the potential role of co-inoculated mosquito saliva on the keratinocyte immune response and viral replication. A type I and III interferon inflammatory response associated with an increase of IRF7 but not IRF3 mRNA expression, and dependent on infectious dose, was observed during keratinocyte infection with WNV. Expression of several interferon-stimulated gene mRNA was also increased at 24 h post-infection (p.i.); they included CXCL10 and interferon-induced proteins with tetratricopeptide repeats (IFIT)-2 sustained up until 48 h p.i. Moreover, WNV infection of keratinocyte resulted in a significant increase of pro-inflammatory cytokines (TNFα, IL-6) and various chemokines (CXCL1, CXCL2, CXCL8 and CCL20) expression. The addition of Aedes aegypti or Culex quinquefasciatus mosquito saliva, two vectors of WNV infection, to infected keratinocytes led to a decrease of inflammatory response at 24 h p.i. However, only Ae. Aegypti saliva adjunction induced modulation of viral replication. In conclusion, this work describes for the first time the inflammatory response of human primary keratinocytes to WNV infection and its modulation in presence of vector mosquito saliva. The effects of mosquito saliva assessed in this work could be involved in the early steps of WNV replication in skin promoting viral spread through the body.

ACS Style

Magali Garcia; Haoues Alout; Fodé Diop; Alexia Damour; Michèle Bengue; Mylene Weill; Dorothée Missé; Nicolas Lévêque; Charles Bodet. Innate Immune Response of Primary Human Keratinocytes to West Nile Virus Infection and Its Modulation by Mosquito Saliva. Frontiers in Cellular and Infection Microbiology 2018, 8, 387 .

AMA Style

Magali Garcia, Haoues Alout, Fodé Diop, Alexia Damour, Michèle Bengue, Mylene Weill, Dorothée Missé, Nicolas Lévêque, Charles Bodet. Innate Immune Response of Primary Human Keratinocytes to West Nile Virus Infection and Its Modulation by Mosquito Saliva. Frontiers in Cellular and Infection Microbiology. 2018; 8 ():387.

Chicago/Turabian Style

Magali Garcia; Haoues Alout; Fodé Diop; Alexia Damour; Michèle Bengue; Mylene Weill; Dorothée Missé; Nicolas Lévêque; Charles Bodet. 2018. "Innate Immune Response of Primary Human Keratinocytes to West Nile Virus Infection and Its Modulation by Mosquito Saliva." Frontiers in Cellular and Infection Microbiology 8, no. : 387.

Research paper
Published: 02 August 2018 in Virulence
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Pseudomonas aeruginosa, an opportunistic pathogen involved in skin and lung diseases, possesses numerous virulence factors, including type 2 and 3 secretion systems (T2SS and T3SS) and its flagellum, whose functions remain poorly known during cutaneous infection. Using isogenic mutants deleted from genes encoding each or all of these three virulence factors, we investigated their role in induction of inflammatory response and in tissue invasiveness in human primary keratinocytes and reconstructed epidermis. Our results showed that flagellum, but not T2SS and T3SS, is involved in induction of a large panel of cytokine, chemokine, and antimicrobial peptide (AMP) mRNA in the infected keratinocytes. Chemokine secretion and AMP tissular production were also dependent on the presence of the bacterial flagellum. This pro-inflammatory effect was significantly reduced in keratinocytes infected in presence of anti-toll-like receptor 5 (TLR5) neutralizing antibody. Bacterial invasion of human epidermis and persistence in a mouse model of sub-cutaneous infection were dependent on the P. aeruginosa flagellum. We demonstrated that flagellum constitutes the main virulence factor of P. aeruginosa involved not only in early induction of the epidermis inflammatory response but also in bacterial invasion and cutaneous persistence. P. aeruginosa is mainly sensed by TLR5 during the early innate immune response of human primary keratinocytes.

ACS Style

Magali Garcia; Eric Morello; Julien Garnier; Christine Barrault; Martine Garnier; Christophe Burucoa; Jean-Claude Lecron; Mustapha Si-Tahar; François-Xavier Bernard; Charles Bodet. Pseudomonas aeruginosa flagellum is critical for invasion, cutaneous persistence and induction of inflammatory response of skin epidermis. Virulence 2018, 9, 1163 -1175.

AMA Style

Magali Garcia, Eric Morello, Julien Garnier, Christine Barrault, Martine Garnier, Christophe Burucoa, Jean-Claude Lecron, Mustapha Si-Tahar, François-Xavier Bernard, Charles Bodet. Pseudomonas aeruginosa flagellum is critical for invasion, cutaneous persistence and induction of inflammatory response of skin epidermis. Virulence. 2018; 9 (1):1163-1175.

Chicago/Turabian Style

Magali Garcia; Eric Morello; Julien Garnier; Christine Barrault; Martine Garnier; Christophe Burucoa; Jean-Claude Lecron; Mustapha Si-Tahar; François-Xavier Bernard; Charles Bodet. 2018. "Pseudomonas aeruginosa flagellum is critical for invasion, cutaneous persistence and induction of inflammatory response of skin epidermis." Virulence 9, no. 1: 1163-1175.

Clinical study
Published: 27 March 2018 in Helicobacter
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Background The pathological determinism of H. pylori infection is explained by complex interplay between bacterial virulence and host inflammatory response. In a large prospective multicenter clinical study, Th17 response, expression of antimicrobial peptides (AMPs), cagA and vacA status, and bacterial density were investigated in the gastric mucosa of H. pylori ‐infected patients. Materials and methods Gastric inflammatory response was analyzed by RT‐qPCR for quantification of Th17 cytokines (IL‐17A, IL‐22), CXCL‐8, and AMPs (BD2 and S100A9) mRNA levels in gastric biopsies. Detection and genotyping of H. pylori strains were achieved by bacterial culture and PCR. Results Among 787 patients screened for H. pylori, 269 were analyzed (147 H. pylori ‐infected and 122 uninfected patients). In H. pylori ‐infected patients, distribution was 83 gastritis, 12 duodenal ulcers, 5 gastric ulcers, and 47 precancerous and cancerous lesions. CXCL‐8, IL‐17A, BD2, and S100A9 mRNA levels were significantly increased in H. pylori ‐infected patients but, surprisingly, IL‐22 was not, and no difference was shown between H. pylori ‐related diseases. A positive correlation was identified between S100A9 expression and bacterial density. Although expression of the virulence genes cagA and vacA did not impact inflammatory response, patients infected with a cagA‐positive strain were associated with severe H. pylori ‐related diseases. Conclusion This study showed that CXCL‐8, IL‐17A, and AMPs are not differently expressed according to the various H. pylori ‐related diseases. The clinical outcome determinism of H. pylori infection is most likely not driven by gastric inflammation but rather tends to mainly influenced by bacterial virulence factors.

ACS Style

Julie Cremniter; Charles Bodet; David Tougeron; Xavier Dray; Joëlle Guilhot; Jean-François Jégou; Franck Morel; Jean-Claude Lecron; Christine Silvain; Christophe Burucoa. Th-17 response and antimicrobial peptide expression are uniformly expressed in gastric mucosa of Helicobacter pylori -infected patients independently of their clinical outcomes. Helicobacter 2018, 23, e12479 .

AMA Style

Julie Cremniter, Charles Bodet, David Tougeron, Xavier Dray, Joëlle Guilhot, Jean-François Jégou, Franck Morel, Jean-Claude Lecron, Christine Silvain, Christophe Burucoa. Th-17 response and antimicrobial peptide expression are uniformly expressed in gastric mucosa of Helicobacter pylori -infected patients independently of their clinical outcomes. Helicobacter. 2018; 23 (3):e12479.

Chicago/Turabian Style

Julie Cremniter; Charles Bodet; David Tougeron; Xavier Dray; Joëlle Guilhot; Jean-François Jégou; Franck Morel; Jean-Claude Lecron; Christine Silvain; Christophe Burucoa. 2018. "Th-17 response and antimicrobial peptide expression are uniformly expressed in gastric mucosa of Helicobacter pylori -infected patients independently of their clinical outcomes." Helicobacter 23, no. 3: e12479.

Article
Published: 01 October 2017 in Reviews in Medical Microbiology
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Zika virus (ZIKV) can be transmitted by the mosquito bite, through blood transfusion, organ transplantation and potentially urine or saliva. From its inoculation site, the virus will spread to various organs such as the central nervous system leading to neurological complications, particularly Guillain–Barré syndrome, or the fetus causing microcephaly. During the infection, ZIKV will have to cross multiple barriers according to the route of transmission and the infection site such as the skin, male and female genital mucosa or blood–brain and placental barriers. At these sites, ZIKV will establish an infection that the innate immune response will try to block before systemic spread occurs to the target organs. The aim of this review is to summarize the knowledge on the mechanisms of anti-ZIKV innate immunity, its characteristics at the different barriers encountered and tissues infected during the infection, and on the escape mechanisms developed by the virus to deal with it.

ACS Style

Vincent Lerat; Magali Garcia; Michel Wehbe; Agnès Beby-Defaux; Charles Bodet; Nicolas Lévêque. Innate immunity against Zika virus. Reviews in Medical Microbiology 2017, 28, 167 -174.

AMA Style

Vincent Lerat, Magali Garcia, Michel Wehbe, Agnès Beby-Defaux, Charles Bodet, Nicolas Lévêque. Innate immunity against Zika virus. Reviews in Medical Microbiology. 2017; 28 (4):167-174.

Chicago/Turabian Style

Vincent Lerat; Magali Garcia; Michel Wehbe; Agnès Beby-Defaux; Charles Bodet; Nicolas Lévêque. 2017. "Innate immunity against Zika virus." Reviews in Medical Microbiology 28, no. 4: 167-174.

Research article
Published: 14 July 2017 in PLOS ONE
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Acute-serum Amyloid A (A-SAA), one of the major acute-phase proteins, is mainly produced in the liver but extra-hepatic synthesis involving the skin has been reported. Its expression is regulated by the transcription factors NF-κB, C/EBPβ, STAT3 activated by proinflammatory cytokines. We investigated A-SAA synthesis by resting and cytokine-activated Normal Human Epidermal Keratinocytes (NHEK), and their inflammatory response to A-SAA stimulation. A-SAA expression was also studied in mouse skin and liver in a model mimicking psoriasis and in the skin and sera of psoriatic and atopic dermatitis (AD) patients. NHEK were stimulated by A-SAA or the cytokines IL-1α, IL-17A, IL-22, OSM, TNF-α alone or in combination, previously reported to reproduce features of psoriasis. Murine skins were treated by imiquimod cream. Human skins and sera were obtained from patients with psoriasis and AD. A-SAA mRNA was quantified by RT qPCR. A-SAA proteins were dosed by ELISA or immunonephelemetry assay. IL-1α, TNF-α and mainly IL-17A induced A-SAA expression by NHEK. A-SAA induced its own production and the synthesis of hBD2 and CCL20, both ligands for CCR6, a chemokine receptor involved in the trafficking of Th17 lymphocytes. A-SAA expression was increased in skins and livers from imiquimod-treated mice and in patient skins with psoriasis, but not significantly in those with AD. Correlations between A-SAA and psoriasis severity and duration were observed. Keratinocytes could contribute to psoriasis pathogenesis via A-SAA production, maintaining a cutaneous inflammatory environment, activating innate immunity and Th17 lymphocyte recruitment.

ACS Style

Elodie Couderc; Franck Morel; Pierre Levillain; Amandine Buffière-Morgado; Magalie Camus; Camille Paquier; Charles Bodet; Jean-François Jégou; Mathilde Pohin; Laure Favot; Martine Garcia; Vincent Huguier; Jiad Mcheik; Corinne Lacombe; Hans Yssel; Gérard Guillet; François-Xavier Bernard; Jean-Claude Lecron. Interleukin-17A-induced production of acute serum amyloid A by keratinocytes contributes to psoriasis pathogenesis. PLOS ONE 2017, 12, e0181486 .

AMA Style

Elodie Couderc, Franck Morel, Pierre Levillain, Amandine Buffière-Morgado, Magalie Camus, Camille Paquier, Charles Bodet, Jean-François Jégou, Mathilde Pohin, Laure Favot, Martine Garcia, Vincent Huguier, Jiad Mcheik, Corinne Lacombe, Hans Yssel, Gérard Guillet, François-Xavier Bernard, Jean-Claude Lecron. Interleukin-17A-induced production of acute serum amyloid A by keratinocytes contributes to psoriasis pathogenesis. PLOS ONE. 2017; 12 (7):e0181486.

Chicago/Turabian Style

Elodie Couderc; Franck Morel; Pierre Levillain; Amandine Buffière-Morgado; Magalie Camus; Camille Paquier; Charles Bodet; Jean-François Jégou; Mathilde Pohin; Laure Favot; Martine Garcia; Vincent Huguier; Jiad Mcheik; Corinne Lacombe; Hans Yssel; Gérard Guillet; François-Xavier Bernard; Jean-Claude Lecron. 2017. "Interleukin-17A-induced production of acute serum amyloid A by keratinocytes contributes to psoriasis pathogenesis." PLOS ONE 12, no. 7: e0181486.

Journal article
Published: 01 June 2017 in European Cytokine Network
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Magali Garcia; Michel Wehbe; Nicolas Lévêque; Charles Bodet. Skin innate immune response to flaviviral infection. European Cytokine Network 2017, 28, 41 -51.

AMA Style

Magali Garcia, Michel Wehbe, Nicolas Lévêque, Charles Bodet. Skin innate immune response to flaviviral infection. European Cytokine Network. 2017; 28 (2):41-51.

Chicago/Turabian Style

Magali Garcia; Michel Wehbe; Nicolas Lévêque; Charles Bodet. 2017. "Skin innate immune response to flaviviral infection." European Cytokine Network 28, no. 2: 41-51.

Journal article
Published: 01 May 2017 in Journal of Ethnopharmacology
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Leaves of Crateva adansonii DC (Capparidaceae), a small bush found in Togo, are widely used in traditional medicine to cure infectious abscesses. Traditional healers of Lomé harvest only budding leaves early in the morning, in specific area in order to prepare their drugs.

ACS Style

Kplolali Ahama-Esseh; Charles Bodet; Akossiwa Quashie-Mensah-Attoh; Magali Garcia; Isabelle Théry-Koné; Joelle Dorat; Comlan De Souza; Cécile Enguehard-Gueiffier; Leslie Boudesocque-Delaye. Anti-inflammatory activity of Crateva adansonii DC on keratinocytes infected by Staphylococcus aureus : From traditional practice to scientific approach using HPTLC-densitometry. Journal of Ethnopharmacology 2017, 204, 26 -35.

AMA Style

Kplolali Ahama-Esseh, Charles Bodet, Akossiwa Quashie-Mensah-Attoh, Magali Garcia, Isabelle Théry-Koné, Joelle Dorat, Comlan De Souza, Cécile Enguehard-Gueiffier, Leslie Boudesocque-Delaye. Anti-inflammatory activity of Crateva adansonii DC on keratinocytes infected by Staphylococcus aureus : From traditional practice to scientific approach using HPTLC-densitometry. Journal of Ethnopharmacology. 2017; 204 ():26-35.

Chicago/Turabian Style

Kplolali Ahama-Esseh; Charles Bodet; Akossiwa Quashie-Mensah-Attoh; Magali Garcia; Isabelle Théry-Koné; Joelle Dorat; Comlan De Souza; Cécile Enguehard-Gueiffier; Leslie Boudesocque-Delaye. 2017. "Anti-inflammatory activity of Crateva adansonii DC on keratinocytes infected by Staphylococcus aureus : From traditional practice to scientific approach using HPTLC-densitometry." Journal of Ethnopharmacology 204, no. : 26-35.

Research article
Published: 05 December 2016 in Innate Immunity
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Inflammatory signaling pathways induced by Helicobacter pylori remain unclear, having been studied mostly on cell-line models derived from gastric adenocarcinoma with potentially altered signaling pathways and nonfunctional receptors. Here, H. pylori-induced signaling pathways were investigated in primary human gastric epithelial cells. Inflammatory response was analyzed on chemokine mRNA expression and production after infection of gastric epithelial cells by H. pylori strains, B128 and B128Δ cagM, a cag type IV secretion system defective strain. Signaling pathway involvement was investigated using inhibitors of epidermal growth factor receptor (EGFR), MAPK, JAK and blocking Abs against TLR2 and TLR4. Inhibitors of EGFR, MAPK and JAK significantly reduced the chemokine mRNA expression and production induced by both H. pylori strains at 3 h and 24 h post-infection. JNK inhibitor reduced chemokine production at 24 h post-infection. Blocking Abs against TLR2 but not TLR4 showed significant reduction of chemokine secretion. Using primary culture of human gastric epithelial cells, our data suggest that H. pylori can be recognized by TLR2, leading to chemokine induction, and that EGFR, MAPK and the JAK/STAT signaling pathways play a key role in the H. pylori-induced CXCL1, CXCL5 and CXCL8 response in a cag pathogenicity island-independent manner.

ACS Style

Cong Tri Tran; Magali Garcia; Martine Garnier; Christophe Burucoa; Charles Bodet. Inflammatory signaling pathways induced by Helicobacter pylori in primary human gastric epithelial cells. Innate Immunity 2016, 23, 165 -174.

AMA Style

Cong Tri Tran, Magali Garcia, Martine Garnier, Christophe Burucoa, Charles Bodet. Inflammatory signaling pathways induced by Helicobacter pylori in primary human gastric epithelial cells. Innate Immunity. 2016; 23 (2):165-174.

Chicago/Turabian Style

Cong Tri Tran; Magali Garcia; Martine Garnier; Christophe Burucoa; Charles Bodet. 2016. "Inflammatory signaling pathways induced by Helicobacter pylori in primary human gastric epithelial cells." Innate Immunity 23, no. 2: 165-174.

Journal article
Published: 01 December 2016 in Annales de Dermatologie et de Vénéréologie
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Magali Garcia; Martine Garnier; Julien Garnier; Christine Barrault; Eric Morello; Mustapha Di-Tahar; Jean Claude Lecron; François Xavier Bernard; Charles Bodet. Rôle majeur du flagelle de Pseudomonas aeruginosa dans l’invasion et l’induction de l’inflammation cutanée. Annales de Dermatologie et de Vénéréologie 2016, 143, S425 -S426.

AMA Style

Magali Garcia, Martine Garnier, Julien Garnier, Christine Barrault, Eric Morello, Mustapha Di-Tahar, Jean Claude Lecron, François Xavier Bernard, Charles Bodet. Rôle majeur du flagelle de Pseudomonas aeruginosa dans l’invasion et l’induction de l’inflammation cutanée. Annales de Dermatologie et de Vénéréologie. 2016; 143 (12):S425-S426.

Chicago/Turabian Style

Magali Garcia; Martine Garnier; Julien Garnier; Christine Barrault; Eric Morello; Mustapha Di-Tahar; Jean Claude Lecron; François Xavier Bernard; Charles Bodet. 2016. "Rôle majeur du flagelle de Pseudomonas aeruginosa dans l’invasion et l’induction de l’inflammation cutanée." Annales de Dermatologie et de Vénéréologie 143, no. 12: S425-S426.

Journal article
Published: 04 September 2016 in Helicobacter
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Human gastric mucosa shows continuous self-renewal via differentiation from stem cells that remain poorly characterized. We describe an original protocol for culture of gastric stem/progenitor cells from adult human stomach. The molecular characteristics of cells were studied using TaqMan low-density array and qRT-PCR analyses using the well-characterized H1 and H9 embryonic stem cells as reference. Epithelial progenitor cells were challenged with H. pylori to characterize their inflammatory response. Resident gastric stem cells expressed specific molecular markers of embryonic stem cells (SOX2, NANOG, and OCT4), as well as others specific to adult stem cells, particularly LGR5 and CD44. We show that gastric stem cells spontaneously differentiate into epithelial progenitor cells that can be challenged with H. pylori. The epithelial progenitor response to H. pylori showed a cag pathogenicity island-dependent induction of matrix metalloproteinases 1 and 3, chemokine (CXCL1, CXCL5, CXCL8, CCL20) and interleukine 33 expression. This study opens new outlooks for investigation of gastric stem cell biology and pathobiology as well as host–H. pylori interactions.

ACS Style

Magali Garcia; Jean Claude Chomel; Pascale Mustapha; Cong Tri Tran; Martine Garnier; Isabelle Paris; Nathalie Quellard; Julie Godet; Julie Cremniter; Annelise Bennaceur Griscelli; Jean-Claude Lecron; Ali Turhan; Christophe Burucoa; Charles Bodet. In vitro culture and phenotypic and molecular characterization of gastric stem cells from human stomach. Helicobacter 2016, 22, e12351 .

AMA Style

Magali Garcia, Jean Claude Chomel, Pascale Mustapha, Cong Tri Tran, Martine Garnier, Isabelle Paris, Nathalie Quellard, Julie Godet, Julie Cremniter, Annelise Bennaceur Griscelli, Jean-Claude Lecron, Ali Turhan, Christophe Burucoa, Charles Bodet. In vitro culture and phenotypic and molecular characterization of gastric stem cells from human stomach. Helicobacter. 2016; 22 (2):e12351.

Chicago/Turabian Style

Magali Garcia; Jean Claude Chomel; Pascale Mustapha; Cong Tri Tran; Martine Garnier; Isabelle Paris; Nathalie Quellard; Julie Godet; Julie Cremniter; Annelise Bennaceur Griscelli; Jean-Claude Lecron; Ali Turhan; Christophe Burucoa; Charles Bodet. 2016. "In vitro culture and phenotypic and molecular characterization of gastric stem cells from human stomach." Helicobacter 22, no. 2: e12351.

Review article
Published: 10 March 2015 in Journal of Natural Products
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Two heterodimers comprising anthraquinone and methylbenzoisocoumarin moieties (1 and 2) were isolated, together with emodin and physcion from the tubers of Pyrenacantha kaurabassana. The structures of 1 and 2 were established by NMR spectroscopy, including the analysis of a 2D INADEQUATE spectrum. On the basis of the data obtained, the structures that were previously proposed in the literature for these compounds were revised. Compounds 1 and 2 showed antibacterial activity against three different strains of Staphylococcus aureus. Compound 2 also showed bactericidal activity against Helicobacter pylori.

ACS Style

Leslie Boudesocque-Delaye; Daniel Agostinho; Charles Bodet; Isabelle Thery-Kone; Hassan Allouchi; Alain Gueiffier; Jean-Marc Nuzillard; Cécile Enguehard-Gueiffier. Antibacterial Polyketide Heterodimers from Pyrenacantha kaurabassana Tubers. Journal of Natural Products 2015, 78, 597 -603.

AMA Style

Leslie Boudesocque-Delaye, Daniel Agostinho, Charles Bodet, Isabelle Thery-Kone, Hassan Allouchi, Alain Gueiffier, Jean-Marc Nuzillard, Cécile Enguehard-Gueiffier. Antibacterial Polyketide Heterodimers from Pyrenacantha kaurabassana Tubers. Journal of Natural Products. 2015; 78 (4):597-603.

Chicago/Turabian Style

Leslie Boudesocque-Delaye; Daniel Agostinho; Charles Bodet; Isabelle Thery-Kone; Hassan Allouchi; Alain Gueiffier; Jean-Marc Nuzillard; Cécile Enguehard-Gueiffier. 2015. "Antibacterial Polyketide Heterodimers from Pyrenacantha kaurabassana Tubers." Journal of Natural Products 78, no. 4: 597-603.