Journal article

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 de Labastida Rivera, Fiona H Amante, Paul J Hertzog, Christian R Engwerda, Laurent Renia, Ashraful Haque



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 ..

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Awarded by Australian National Health and Medical Research Council

Awarded by National Research Foundation Singapore

Funding Acknowledgements

The authors gratefully acknowledge assistance from the staff of the QIMR Berghofer Animal Facility for animal husbandry, and the QIMR Berghofer Flow Cytometry facility for assistance in flow cytometry. We thank Poh Chek Meng (SIgN) and Dr Gjis Grotenbreg (National University of Singapore) for providing the PbA-specific MHC tetramers. This work was supported by grants (GRNTs 613702, 1028641, and 1028634 (AH), and 496600 (CRE)) from the Australian National Health and Medical Research Council and by an intramural grant from Singapore's Agency for Science, Technology and Research and the National Research Foundation Singapore under its Research Fellowship Programme (NRF2007NRF-RF001-226). Sin Yee Gun is supported by a postgraduate scholarship from the Yong Loo Lin School of Medicine, National University of Singapore (Singapore). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.