A role for natural killer cells in intestinal inflammation caused by infection with Salmonella enterica serovar Typhimurium.
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-gamma) 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-gamma 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-gamma production and the numbers of NK cells in the intestine and mesenteric lymph nodes. NK cells, along with other types of lymphocytes, produced IFN-gamma 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-gamma expression. In a mouse strain lacking NK cells and T and B lymphocytes, intestinal production of IFN-gamma and Salmonella-induced 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-gamma in regulating the intestinal inflammatory response to Salmonella.
Harrington
Lynne
L
Mucosal Immunology Laboratory, Pediatric Gastroenterology Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Srikanth
Chittur V
CV
Antony
Reuben
R
Shi
Hai Ning
HN
Cherayil
Bobby J
BJ
D000818:Animals; D005759:Gastroenteritis / Q000382:microbiology / Q000473:pathology*; D007249:Inflammation / Q000473:pathology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007422:Intestines / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology*; D047589:Leukocyte Reduction Procedures; D008198:Lymph Nodes / Q000473:pathology; D008640:Mesenteric Lymphadenitis / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D012480:Salmonella Infections / Q000473:pathology*; D012486:Salmonella typhimurium / Q000276:immunology*
D007371:Interferon-gamma