PhD defence: Issam Tout

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Date / Heure
Date(s) - 15/12/2017
14 h 00 min - 17 h 00 min

Amphi Pasteur, Tour CERVI

PhD defence: Issam ToutInnate immunity in infectious and autoimmune diseases (CIRI) and Hepatocarcinogenesis and viral infection (CRCL)


Title : “The role of TLR9 and B cells in innate immune escape by hepatitis B virus


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.

Keywords : Chronic infection, HBV, B cells, TLR9, CREB



Dr. Olivier DIAZ                     MCU         CIRI             Président du Jury/examinateur

Dr. Laurence CHAPEROT          DR2          IAB              Rapporteur

Dr. Pierre ROQUES                 DR2          CEA              Rapporteur

Dr. Patrick SOUSSAN              MCU-PH     CIMI             Examinateur

Dr. Isabelle CHEMIN               DR2          CRCL            Directeur de thèse

Dr. Uzma HASAN                   CR2          CIRI             Co-directeur de thèse