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: Chin-Yu Chen (陳謦伃)                         Time: 13:10~14:00, Dec. 19, 2012

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

Abstract:

The innate immune system produce type I interferon (IFN) to limit viral replication during systemic infection. In addition to controlling viral replication, cells of the innate immune response initiate the priming of cells of the adaptive immune response. As the amount of presented antigen and replication-incompetent virus limit the adaptive immune response¹, the authors hypothesized existence of a specific compartment that would promote viral replication and increase the presented antigen to improve the adaptive immune response. Previous study showed that CD169⁺ metallophilicmacrophages of the spleen marginal zone present captured viral antigen directly to B cells². In this study, the authors used mouse vesicular stomatitis virus (VSV) and found that CD169⁺ macrophages in the marginal zone of the spleen formed a compartment of enhanced viral replication. CD169⁺macrophages captured virus but did not respond to type I interferon and thus allowed anatomically restricted viral replication in the splenic marginal zone. And they also showed that Usp18 was essential for the enforced replication of VSV in CD169⁺ macrophages. In conclusion, this study suggest that enforced viral replication was triggered by Usp18 expression in CD169⁺ metallophilic macrophages and  required for efficient T cells and B cell response to provide sufficient antigen for effective activation of the adaptive immune response.

References:

1.         Zinkernagel RM. Localization dose and time of antigens determine immune reactivity. Seminars in immunology 2000, 12(3): 163-171; discussion 257-344.

2.         Junt T, Moseman EA, Iannacone M, Massberg S, Lang PA, Boes M, et al. Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B cells. Nature 2007, 450(7166): 110-114.