IL-17-producing γδ T cells protect against Clostridium difficile infection

Yee Shiuan Chen, Iuan Bor Chen, Giang Pham, Tzu Yu Shao, Hansraj Bangar, Sing Sing Way, David B. Haslam

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Colitis caused by Clostridium difficile infection is a growing cause of human morbidity and mortality, especially after antibiotic use in health care settings. The natural immunity of newborn infants and protective host immune mediators against C. difficile infection are not fully understood, with data suggesting that inflammation can be either protective or pathogenic. Here, we show an essential role for IL-17A produced by γδ T cells in host defense against C. difficile infection. Fecal extracts from children with C. difficile infection showed increased IL-17A and T cell receptor γ chain expression, and IL-17 production by intestinal γδ T cells was efficiently induced after infection in mice. C. difficile-induced tissue inflammation and mortality were markedly increased in mice deficient in IL-17A or γδ T cells. Neonatal mice, with naturally expanded RORγt+ γδ T cells poised for IL-17 production were resistant to C. difficile infection, whereas elimination of γδ T cells or IL-17A each efficiently overturned neonatal resistance against infection. These results reveal an expanded role for IL-17-producing γδ T cells in neonatal host defense against infection and provide a mechanistic explanation for the clinically observed resistance of infants to C. difficile colitis.

Original languageEnglish (US)
Pages (from-to)2377-2390
Number of pages14
JournalJournal of Clinical Investigation
Volume130
Issue number5
DOIs
StatePublished - May 1 2020
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint

Dive into the research topics of 'IL-17-producing γδ T cells protect against Clostridium difficile infection'. Together they form a unique fingerprint.

Cite this