1. Enterocyte–innate lymphoid cell crosstalk drives early IFN-γ-mediated control of Cryptosporidium
- Author
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Christopher A. Hunter, David A. Christian, Zachary A Hutchins, Masahiro Yamamoto, Julie B. Engiles, Daniel P. Beiting, Alexis R. Gibson, Gregory A. Taylor, Jodi A. Gullicksrud, Sebastian Shaw, Lindsay Martin, Boris Striepen, and Adam Sateriale more...
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Enterocyte ,Immunology ,Cryptosporidiosis ,Cryptosporidium ,Intestinal parasite ,medicine.disease_cause ,Mice ,Immune system ,medicine ,Animals ,Humans ,Immunology and Allergy ,Lymphocytes ,STAT1 ,Cryptosporidium parvum ,biology ,Effector ,Innate lymphoid cell ,biology.organism_classification ,Immunity, Innate ,Cell biology ,Crosstalk (biology) ,Enterocytes ,medicine.anatomical_structure ,biology.protein - Abstract
The intestinal parasite, Cryptosporidium, is a major contributor to global child mortality and causes opportunistic infection in immune deficient individuals. Innate resistance to Cryptosporidium, which specifically invades enterocytes, is dependent on the production of IFN-γ, yet whether enterocytes contribute to parasite control is poorly understood. In this study, utilizing a mouse-adapted strain of C. parvum, we show that epithelial-derived IL-18 synergized with IL-12 to stimulate innate lymphoid cell (ILC) production of IFN-γ required for early parasite control. The loss of IFN-γ-mediated STAT1 signaling in enterocytes, but not dendritic cells or macrophages, antagonized early parasite control. Transcriptional profiling of enterocytes from infected mice identified an IFN-γ signature and enrichment of the anti-microbial effectors IDO, GBP, and IRG. Deletion experiments identified a role for Irgm1/m3 in parasite control. Thus, enterocytes promote ILC production of IFN-γ that acts on enterocytes to restrict the growth of Cryptosporidium. more...
- Published
- 2022
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