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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Gullicksrud, JA; Sateriale, A; Engiles, JB; Gibson, AR; Shaw, S; Hutchins, ZA; Martin, L; Christian, DA; Taylor, GA; Yamamoto, M; Beiting, DP; Striepen, B; Hunter, CA

Published Date

  • February 2022

Published In

Volume / Issue

  • 15 / 2

Start / End Page

  • 362 - 372

PubMed ID

  • 34750455

Pubmed Central ID

  • PMC8881313

Electronic International Standard Serial Number (EISSN)

  • 1935-3456

Digital Object Identifier (DOI)

  • 10.1038/s41385-021-00468-6


  • eng

Conference Location

  • United States