Time and space matters in virus infection fate regulation

Acute infection and chronic infection are the two most common fates of pathogenic virus infections. Using the experimental lymphocytic choriomeningitis virus (LCMV) infection model of mice, we show that a temporal difference in cytotoxic T cell-mediated killing of splenic marginal zone CD169+ macrophages is a critical event determining the outcome of the infection. It occurs later in acute infection and thus enables CD169+ marginal zone macrophages to produce a type-I interferon wave that is required for generation of effector CD8+ T cells and virus clearance. However, this comes at a cost for the host in the form of spleen fibrosis. Our findings demonstrate the critical importance of kinetically well coordinated sequential immune events for virus infection control.