Enterocyte-innate lymphoid cell crosstalk drives early IFN-γ-mediated control of Cryptosporidium

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-gamma, 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-gamma required for early parasite control. The loss of IFN-gamma-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-gamma 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-gamma that acts on enterocytes to restrict the growth of Cryptosporidium.

Automated summary

This study found that enterocytes promote ILC production of IFN-gamma that acts on enterocytes to restrict the growth of Cryptosporidium. The loss of IFN-gamma-mediated STAT1 signaling in enterocytes is crucial for early parasite control. Transcriptional profiling of infected mice enterocytes identified an IFN-gamma signature and enrichment of anti-microbial effectors.