Spatiotemporal requirements for IRF7 in mediating type I IFN‐dependent susceptibility to blood‐stage Plasmodium infection. Issue 1 (13th November 2014)

• Record Type: Journal Article
• Authors: Edwards, Chelsea L.; Best, Shannon E.; Gun, Sin Yee; Claser, Carla; James, Kylie R.; de Oca, Marcela Montes; Sebina, Ismail; Rivera, Fabian de Labastida; Amante, Fiona H.; Hertzog, Paul J.; Engwerda, Christian R.; Renia, Laurent; Haque, Ashraful
• Is Part Of: European journal of immunology. Volume 45:Issue 1(2015)
• Page Start: 130
• Page End: 141
• Publication Date: 2014-11-13
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201444824
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Type I IFN signaling suppresses splenic T helper 1 (Th1) responses during blood‐stage <italic>Plasmodium berghei</italic> ANKA (<italic>Pb</italic>A) 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 <italic>Pb</italic>A infection and nonlethal <italic>Plasmodium chabaudi chabaudi</italic> AS (<italic>Pc</italic>AS) 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 <italic>Pb</italic>A infection. Finally, IRF7 also suppressed antiparasitic immunity and Th1 responses during nonlethal <italic>Pc</italic>AS 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.</p> </abstract>