Interaction between macrophages, hepatocytes and hepatitis B virus : from reprogramming of macrophages phenotypes towards establishment and maintenance of the infection

Abstract : Hepatitis B virus (HBV) chronically infects over 250 million people worldwide. Several treatments can be used to prevent the formation of de novo particles. However, they do not allow the total eradication of the infection. Therefore, it is necessary to develop new therapeutic strategies, including immune-therapeutic ones, which would be more likely to lead to an immunological control of HBV infections. We have recently shown that IL-1ß is the most effective antiviral cytokine against the replication of HBV in vitro. In the liver, IL-1ß is mainly produced by resident macrophages (also called Kupffer cells) or infiltrating cells (inflammatory monocytes differentiated into macrophages). Recent studies have shown that HBV is able to partially inhibit the induction of innate immune responses. Hence, it was necessary to determine if HBV was also able to block the production of IL-1ß by the different types of macrophages.The objective of this thesis was to study the effect of HBV on macrophage phenotypes and the impact of those modifications on the establishment of HBV infection in hepatocytes.Blood monocytes and liver macrophages were purified, respectively, from peripheral blood or hepatic resections, and were exposed to HBV during their differentiation and/or activation for monocytes, or only during activation for liver macrophages which are already in a differentiated state. HBV was able to partially inhibit the secretion of IL-6 and IL-1ß by pro-inflammatory macrophages. Moreover, HBV was able to inhibit IL-1ß secretion by liver macrophages stimulated by different ligands and, conditioned medium of pro-inflammatory macrophages could inhibit the establishment of infection in hepatocytes. This effect was reverted when macrophages were exposed to HBV, concomitantly with a lower production of IL-6 and IL-1ß.In summary, HBV is able to modify macrophage phenotypes to favour the establishment and persistence of HBV infection. The full understanding of the mechanistic basis of how HBV phenotypically modifies macrophages will be a first step towards the development of new therapeutic strategies
Document type :
Theses
Virology. Université de Lyon, 2018. English. 〈NNT : 2018LYSE1073〉
Liste complète des métadonnées

https://tel.archives-ouvertes.fr/tel-01812772
Contributor : Abes Star <>
Submitted on : Monday, June 11, 2018 - 6:14:23 PM
Last modification on : Tuesday, June 12, 2018 - 1:19:46 AM

File

TH2018FAUREDUPUYSUZANNE.pdf
Version validated by the jury (STAR)

Identifiers

  • HAL Id : tel-01812772, version 1

Collections

Citation

Suzanne Faure-Dupuy. Interaction between macrophages, hepatocytes and hepatitis B virus : from reprogramming of macrophages phenotypes towards establishment and maintenance of the infection. Virology. Université de Lyon, 2018. English. 〈NNT : 2018LYSE1073〉. 〈tel-01812772〉

Share

Metrics

Record views

119

Files downloads

22