Beta7 integrin-deficient mice: delayed leukocyte recruitment and attenuated protective immunity in the small intestine during enteric helminth infection.
The ontogeny and function of gut-associated-lymphoid tissue is known to be critically dependent on the beta7 integrin subfamily. We have investigated the development of intestinal inflammation and pathogen-specific protective immunity to enteric helminth infection in beta7 integrin knockout (KO) mice. During Trichinella spiralis infection of the small intestine there was a significant delay and reduction in the magnitude of intestinal eosinophilia and mastocytosis in the absence of P7 integrin, resulting in impaired host protection. Aberrant distribution of mast cells was also observed in the small intestine of infected KO mice. Adoptive transfer of primed wild-type mesenteric lymph node cells into T. spiralis-infected beta7 KO mice did not restore the intestinal mast cell response, suggesting that the defect in intestinal mastocytosis is due to the absence of beta7 expression on this population rather than an indirect consequence of reduced T cell numbers. In contrast, no impairment in leukocyte recruitment or protection against Trichuris muris infection of the large intestine was observed in KO mice. Taken together the data provide the first description of reduced leukocyte homing and attenuated protective immunity against helminth infection in beta7 KO mice. Furthermore, these results suggest that beta7 integrin-independent adhesion molecule interactions are deployed in the large but not small intestine during intestinal inflammation.
Artis
D
D
Immunology Group, School of Biological Sciences, University of Manchester, GB.
Humphreys
N E
NE
Potten
C S
CS
Wagner
N
N
Müller
W
W
McDermott
J R
JR
Grencis
R K
RK
Else
K J
KJ
D000818:Animals; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D039641:Integrin beta Chains; D016023:Integrins / Q000235:genetics / Q000276:immunology*; D007411:Intestinal Diseases, Parasitic / Q000276:immunology* / Q000473:pathology; D007421:Intestine, Small / Q000276:immunology* / Q000473:pathology; D007962:Leukocytes / Q000166:cytology / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology; D008415:Mastocytosis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017160:Trichinella spiralis / Q000276:immunology*; D014235:Trichinellosis / Q000276:immunology* / Q000473:pathology
D039641:Integrin beta Chains; D016023:Integrins; C091368:integrin beta7