Leucocyte recruitment during enteric nematode infection.
Resolution of infection with the intestinal nematode Trichinella spiralis depends on the host mounting a T helper 2 (Th2) response. It is known that both mast cells and T cells play a crucial role. We have previously shown that efficient migration of mast cells to the gut during infection depends on their expression of the integrin beta 7. beta 7 forms a heterodimer complex with either alpha E or alpha 4 integrin chains, alpha E beta 7 binding to E-cadherin expressed by epithelial cells and alpha 4 beta 7 binding to mucosal addressin cell adhesion molecule (MAdCAM-1) on the endothelium. We were interested to know whether dysfunctional mast cell localization to the gut in the absence of beta 7 was due to the failure of alpha 4 beta 7 to bind to MAdCAM-1 or the failure of alpha E beta 7 to bind to E-cadherin. We used blocking monoclonal antibodies against alpha E (M290) or alpha 4 (PS2) or beta 7 (HB293) during T. spiralis infection of C57BL/6 mice and found that all antibody treatments reduced mastocytosis. In contrast, none of the antibody treatments prevented the migration of CD3(+) T cells into the intestine. These results indicate that during inflammation (a) there is integrin redundancy for lymphocytes but not for mast cells and (b) both alpha E beta 7 and alpha 4 beta 7 are crucial either for the entry of mast cells into the gut or for their maturation once they have entered.
McDermott
J R
JR
Immunology Group, School of Biological Sciences, Stopford Building, Oxford Road, University of Manchester, Manchester, UK. jacqueline.r.mcdermott@man.ac.uk
Grencis
R K
RK
Else
K J
KJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001667:Binding, Competitive; D002465:Cell Movement / Q000276:immunology; D004802:Eosinophilia / Q000276:immunology; D020397:Goblet Cells / Q000276:immunology / Q000473:pathology; D006965:Hyperplasia / Q000276:immunology; D016023:Integrins / Q000276:immunology; D007411:Intestinal Diseases, Parasitic / Q000276:immunology*; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D008415:Mastocytosis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016176:T-Lymphocyte Subsets / Q000276:immunology; D017160:Trichinella spiralis; D014235:Trichinellosis / Q000276:immunology*
D000911:Antibodies, Monoclonal; D016023:Integrins