Type I interferons regulate immune responses in humans with blood-stage Plasmodium falciparum infection

de Oca, Marcela Montes, Kumar, Rajiv, Rivera, Fabian de Labastida, Amante, Fiona H., Sheel, Meru, Faleiro, Rebecca J., Bunn, Patrick T., Best, Shannon E., Beattie, Lynette, Ng, Susanna S., Edwards, Chelsea L., Boyle, Glen M., Price, Ric N., Anstey, Nicholas M., Loughland, Jessica R., Burel, Julie, Doolan, Denise, Haque, Ashraful, McCarthy, James S., and Engwerda, Christian R. (2016) Type I interferons regulate immune responses in humans with blood-stage Plasmodium falciparum infection. Cell Reports, 17 (2). pp. 399-412.

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Abstract

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 antiparasitic 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 IFN gamma 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.

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