Type I Interferons Regulate Immune Responses in Humans with Blood-Stage Plasmodium falciparum Infection

The development of immunoregulatory networks is important to prevent disease. However, these same networks allow pathogens to persist and reduce vaccine efficacy. Here, we identify type I interferons (IFNs) as important regulators in developing anti-parasitic immunity in healthy volunteers infected for the first time with Plasmodium falciparum. Type I IFNs suppressed innate immune cell function and parasitic-specific CD4+ T cell IFNγ production, and they promoted the development of parasitic-specific IL-10-producing Th1 (Tr1) cells. Type I IFN-dependent, parasite-specific IL-10 production was also observed in P. falciparum malaria patients in the field following chemoprophylaxis. Parasite-induced IL-10 suppressed inflammatory cytokine production, and IL-10 levels after drug treatment were positively associated with parasite burdens before anti-parasitic drug administration. These findings have important implications for understanding the development of host immune responses following blood-stage P. falciparum infection, and they identify type I IFNs and related signaling pathways as potential targets for therapies or vaccine efficacy improvement. [Display omitted] •Plasmodium falciparum-induced type I IFNs suppress Th1 cell development•Type I IFNs promote development of parasite-specific IL-10-producing Th1 (Tr1) cells•Chemoprophylaxis stimulates type I IFN-dependent, parasite-specific IL-10 production•Parasite-induced IL-10 suppresses inflammatory cytokine production Eliminating pathogens requires inflammation and immune regulation. Montes de Oca et al. show that type I interferons (IFNs) suppress innate and adaptive immunity and promote IL-10-producing CD4+ T cells in controlled human malaria infection studies. These results provide a potential explanation for why vaccines may function sub-optimally in disease-endemic areas.