Marcela Montes de Oca 1 , 2 , Rajiv Kumar 1 , 3 , Fabian de Labastida Rivera 1 , Fiona H. Amante 1 , Meru Sheel 1 , Rebecca J. Faleiro 1 , 4 , Patrick T. Bunn 1 , 5 , Shannon E. Best 1 , Lynette Beattie 1 , Susanna S. Ng 1 , 6 , Chelsea L. Edwards 1 , 2 , Glen M. Boyle 1 , Ric N. Price 7 , 8 , 9 , Nicholas M. Anstey 7 , 8 , Jessica R. Loughland 7 , 8 , Julie Burel 1 , Denise L. Doolan 1 , Ashraful Haque 1 , James S. McCarthy 1 , 2 , * , Christian R. Engwerda 1 , *
27 October 2016
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.