| Title: |
The role of TLR9 and B cells in innate immune escape by hepatitis B virus ; Rôle du TLR9 et des lymphocytes B dans l'échappement du virus de l'hépatite B à l'immunité innée |
| Authors: |
Tout, Issam |
| Contributors: |
Réponse immunitaire innée dans les maladies infectieuses et auto-immunes – Innate immunity in infectious and autoimmune diseases CIRI; Centre International de Recherche en Infectiologie (CIRI); École normale supérieure de Lyon (ENS de Lyon); Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon); Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Université de Lyon; Isabelle Chemin; Uzma Hasan |
| Source: |
https://theses.hal.science/tel-01781861 ; Immunologie. Université de Lyon, 2017. Français. ⟨NNT : 2017LYSE1308⟩. |
| Publisher Information: |
CCSD |
| Publication Year: |
2017 |
| Collection: |
Université Jean Monnet – Saint-Etienne: HAL |
| Subject Terms: |
CREB; TLR9; B cells; HBV; Chronic infection; Cellules B; Infection chronique; [SDV.IMM]Life Sciences [q-bio]/Immunology |
| Description: |
Chronic HBV infection is a major health problem worldwide. Ineffective T cell and antibody responses have been demonstrated, yet the precise events that may contribute to insufficient B cell responses remain to be determined. Optimal B cell function, expansion and differentiation rely on Toll Like Receptor 9 (TLR9) activity which senses dsDNA and is expressed in human mainly by plasmacytoid dendritic ( pDC) and B cells. The impact of HBV on TLR9 in human B cell subsets remains to be explored.Here, we investigated the effects of HBV on TLR9 function in human B cells. Both primary and B cell lines were used to analyze the effect of HBV on TLR9 expression and function. These results were corroborated in a cohort of chronically infected HBV patients. TLR9 expression was reduced in all peripheral blood B cells subsets exposed to HBV. B cell function mediated by TLR9, such as proliferation and pro-inflammatory cytokines secretion were abrogated in the presence of HBV. Our results show that the viral surface antigen HBsAg inhibited the phosphorylation of the transcription factor CREB which could no longer bind the CRE site located on the TLR9 promoter. Finally, we corroborated our in vitro findings in a cohort of chronic HBV carriers (CHB) and found that TLR9 expression and function were significantly suppressed.Our findings reveal the mechanism that induces an immunosuppressive response by HBV on TLR9 function in human B cells, which may contribute to HBV persistence in the host ; L'infection chronique par le virus de l’hépatite B (HBV) est un problème de santé majeur dans le monde et peut conduire à la cirrhose et à l’hépatocarcinome. Des réponses défectives des cellules T ont été démontrées, mais les événements précis qui peuvent contribuer à l'insuffisance des réponses des cellules B restent à déterminer. L'expansion et la différenciation optimales des cellules B reposent sur l'activité du récepteur Toll Like Receptor 9 (TLR9) qui détecte l'ADNdb et est exprimée chez l'homme principalement par les cellules ... |
| Document Type: |
doctoral or postdoctoral thesis |
| Language: |
French |
| Relation: |
NNT: 2017LYSE1308 |
| Availability: |
https://theses.hal.science/tel-01781861; https://theses.hal.science/tel-01781861v1/document; https://theses.hal.science/tel-01781861v1/file/TH2017TOUTISSAM.pdf |
| Rights: |
https://about.hal.science/hal-authorisation-v1/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.45A3CD1E |
| Database: |
BASE |