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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

73 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)399-412
Number of pages14
JournalCell Reports
Volume17
Issue number2
DOIs
Publication statusPublished - 4 Oct 2016
Externally publishedYes

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