Th17 cells enhance viral persistence and inhibit T cell cytotoxicity in a model of chronic virus infection

Hou, W., et al. 2009. J. Exp Med. 206, 313-328

Speaker: Jhen-Yu Ke (柯貞妤)                                  Time:15:00~16:00, May 6, 2009

Commentator: Dr. Yao Chang (張 堯 老師)          Place: Room 601

Abstract:

        Infection with viruses that have the capacity to modulate or evade the immune response can result in persistency, which can lead to a variety of chronic diseases¹. During viral persistency, the balance between the virus and the host immune response is crucial. However,in the pathogenesis of persistent viral infection, the role of IL-17-producing CD4⁺ T helper (Th17) cells, which can protect host from bacterial or fungal infections², remains unknown. In this paper, the authors found that chronic Theiler’s murine encephalomyelitis virusinfection in vitro and in vivo favored Th17 development in an IL-6-dependent manner. The experimental result of anti-IL-17 antibody treatment indicated that Th17 cells secrete IL-17 to promote persistent viral infection and induce the pathogenesis of chronic demyelinating disease. IL-17 enhances inflammatory responses by amplifying virus-induced production of inflammatory cytokines and protects against infection-induced cell apoptosis by up-regulating the expression of antiapoptotic molecules. One interesting finding in this study is that IL-17 impairs antiviral cytotoxic CD8⁺ T cell responses resulting in enhanced viral replication and persistency. Collectively, these observations show the novel pathogenic role of Th17 cells and IL-17 in the persistency of Theiler’s murine encephalomyelitis virus infection.This particular interaction may also potentially operate in other chronic viral infections and could be a target for therapeutic involvement.

References:

1.      Trottier, M., et al. 2004. Transition from acute to persistent Theiler’s virus infection requires active viral replication that drives proinflammatory cytokine expression and chronic demyelinating disease. J. Virol. 78, 12480-12488

2.      Bettelli, E., et al. 2008. Induction and effector functions of T(H)17 cells. Nature 453, 1051-1057