Type I Interferons Induce T Regulatory 1 Responses and Restrict Humoral Immunity during Experimental Malaria

Cd4 t cell-dependent antibody responses are essential for limiting plasmodium parasite replication and the severity of malaria; however,the factors that regulate humoral immunity during highly inflammatory,th1-biased systemic infections are poorly understood. using genetic and biochemical approaches,we show that plasmodium infection-induced type i interferons limit t follicular helper accumulation and constrain anti-malarial humoral immunity. mechanistically we show that cd4 t cell-intrinsic type i interferon signaling induces t-bet and blimp-1 expression,thereby promoting t regulatory 1 responses. we further show that the secreted effector cytokines of t regulatory 1 cells,il-10 and ifn-γ,collaborate to restrict t follicular helper accumulation,limit parasite-specific antibody responses,and diminish parasite control. this circuit of interferon-mediated blimp-1 induction is also operational during chronic virus infection and can occur independently of il-2 signaling. thus,type i interferon-mediated induction of blimp-1 and subsequent expansion of t regulatory 1 cells represent generalizable features of systemic,inflammatory th1-biased viral and parasitic infections that are associated with suppression of humoral immunity. © 2016 zander et al.