Colitis caused by C. difficile infection is an increasing cause of human morbidity and mortality, especially after antibiotic use in healthcare 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 of 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 each significantly increased in mice deficient in IL-17A or γδ T cells. neonatal mice, with naturally expanded ROR-γ+ γδ T cells poised for IL-17 production were resistant to C. difficile infection, whereas eliminating 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.
Yee-Shiuan Chen, Iuan-Bor Chen, Giang Pham, Tzu-Yu Shao, Hansraj Bangar, Sing Sing Way, David B. Haslam