Enforced viral replication activates adaptive immunity and is essential for the control of a cytopathic virus

Honke, N. et al. Nat. Immunol. 13, 51-57 (2012)

Speaker: Fu-I Tsai (蔡馥儀)                                  Time: 15:10~16:00, Mar. 7, 2012

Commentator: Dr. Shun-Hua Chen (陳舜華)       Place: Room 601

Abstract:

In respond to systemic viral infection, the innate immunity produces type I interferon (IFN) to suppress viral replication, and cells in the secondary lymphoid organs capture and present viral antigen to T cells or B cells to activate adaptive immunity. Previous study showed that CD169⁺metallophilic macrophages in spleen marginal zone present captured viral antigen directly to B cells¹. As the amount of antigen and replication-incompetent virus have been shown to limit the adaptive immune response², the authors hypothesized the existence of a specific compartment that allow virus replication and increase the presented antigen to improve the adaptive immune response. First, they found that CD169⁺ macrophage in spleen marginal zone can resist the effect of type I IFN to allow viral replication while the other tissues suppress viral replication in a type I IFN-dependent manner. Furthermore, they showed that USP18, a potent inhibitor of type I IFN³, was essential for the enforced replication of VSV in CD169⁺ macrophages. Finally, they demonstrated that VSV replication in the spleen is required for efficient T cells and B cell response, and defective induction of the adaptive immune response leads to the spread of VSV in to the central nervous system. In conclusion, this study suggested that USP18 allow viral replication in CD169⁺ macrophages to provide sufficient antigen for effective activation of the adaptive immune response.

References:

1. Junt, T. et al. Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B cells. Nature 450, 110–114 (2007).

2. Bachmann, M.F. et al. Immunogenicity of a viral model vaccine after different inactivation procedures. Med. Microbiol. Immunol. (Berl.) 183, 95–104 (1994).

3. Malakhova, O.A. et al. UBP43 is a novel regulator of interferon signaling independent of its ISG15 isopeptidase activity. EMBO J. 25, 2358–2367 (2006).