A role for natural killer cells in intestinal in£ammation caused by infectionwithSalmonella enterica serovarTyphimurium

Acute gastroenteritis caused by Salmonella infection is a significant public health problem. Using a mouse model of this condition, the authors demonstrated previously that the cytokine gamma interferon (IFN-g) is required for a normal intestinal inflammatory response to the pathogen. In the present study, these experiments are extended to show that natural killer (NK) cells constitute an early source of intestinal IFN-g during Salmonella infection, and that these cells have a significant impact on intestinal inflammation. It was found that infection of mice with Salmonella increased both intestinal IFN-g production and the numbers of NK cells in the intestine and mesenteric lymph nodes. NK cells, along with other types of lymphocytes, produced IFN-g in response to the bacteria in vitro, while antibody-mediated depletion of NK cells in vivo resulted in a significant reduction in Salmonella-induced intestinal IFN-g expression. In a mouse strain lacking NK cells and T and B lymphocytes, intestinal production of IFN-g and Salmonellainduced intestinal inflammation were both significantly decreased compared with a strain deficient only in T and B cells. The authors’ observations point to an important function for NK cells and NK-derived IFN-g in regulating the intestinal inflammatory response to Salmonella.