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

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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 L
Haque, Ashraful
McCarthy, James S
Engwerda, Christian R
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2016
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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.

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Cell Reports

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17

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2

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© 2016 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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Biochemistry and cell biology

Biochemistry and cell biology not elsewhere classified

Medical physiology

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