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

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 gamma delta 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 gamma chain expression, and IL-17 production by intestinal gamma delta 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 gamma delta T cells. Neonatal mice, with naturally expanded ROR gamma t(+) gamma delta T cells poised for IL-17 production were resistant to C. difficile infection, whereas elimination of gamma delta T cells or IL-17A each efficiently overturned neonatal resistance against infection. These results reveal an expanded role for IL-17-producing gamma delta T cells in neonatal host defense against infection and provide a mechanistic explanation for the clinically observed resistance of infants to C. difficile colitis.