Spatiotemporal requirements for IRF7 in mediating type I IFN-dependent susceptibility to blood-stage Plasmodium infection

Chelsea L Edwards, Shannon E Best, Sin Yee Gun, Carla Claser, Kylie R James, Marcela Montes de Oca, Ismail Sebina, Fabian Rivera de Labastida Rivera, Fiona H Amante, Paul John Hertzog, Christian R Engwerda, Laurent Renia, Ashraful K M Nazmul Haque

Research output: Contribution to journalArticleResearchpeer-review

11 Citations (Scopus)

Abstract

Type I IFN signaling suppresses splenic T helper 1 (Th1) responses during blood-stage Plasmodium berghei ANKA (PbA) infection in mice, and is crucial for mediating tissue accumulation of parasites and fatal cerebral symptoms via mechanisms that remain to be fully characterized. Interferon regulatory factor 7 (IRF7) is considered to be a master regulator of type I IFN responses. Here, we assessed IRF7 for its roles during lethal PbA infection and nonlethal Plasmodium chabaudi chabaudi AS (PcAS) infection as two distinct models of blood-stage malaria. We found that IRF7 was not essential for tissue accumulation of parasites, cerebral symptoms, or brain pathology. Using timed administration of anti-IFNAR1 mAb, we show that late IFNAR1 signaling promotes fatal disease via IRF7-independent mechanisms. Despite this, IRF7 significantly impaired early splenic Th1 responses and limited control of parasitemia during PbA infection. Finally, IRF7 also suppressed antiparasitic immunity and Th1 responses during nonlethal PcAS infection. Together, our data support a model in which IRF7 suppresses antiparasitic immunity in the spleen, while IFNAR1-mediated, but IRF7-independent, signaling contributes to pathology in the brain during experimental blood-stage malaria.
Original languageEnglish
Pages (from-to)130 - 141
Number of pages12
JournalEuropean Journal of Immunology
Volume45
Issue number1
DOIs
Publication statusPublished - 2015

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