Mechanisms of leucocyte recruitment to the inflamed large intestine: redundancy in integrin and addressin usage.
The caecal-dwelling nematode Trichuris muris provides a natural model of human whipworm infection. Resistance to T. muris is dependent on a host Th2 response, and CD4+Th2 cells migrate to the gut-associated lymphoid tissue (GALT) to elicit parasite expulsion. Thus, CD4+T cells infiltrate the caecal lamina propria during infection, along with other leucocyte subsets that are not critical for parasite expulsion, such as eosinophils. Trafficking of leucocytes to the GALT has been shown to be dependent on the alpha4beta7/MAdCAM-1 integrin-addressin interaction. However, where inflammation is present, such as during T. muris infection, redundant mechanisms of leucocyte recruitment may also occur in addition to traditional gut-homing interactions. We utilized an anti-integrin/addressin antibody treatment regime to investigate this redundancy in resistant, T. muris-infected C57BL/6 mice. Where only the alpha4beta7/MAdCAM-1 interaction was blocked, mice remained resistant to T. muris infection, making a Th2 response and both CD4+T cells and eosinophils infiltrated the site of infection. However, in the absence of available alpha4beta7 and alpha4beta1, mice became chronically infected with T. muris and mounted a more Th1-biased immune response. Interestingly, CD4+T cells, but not eosinophils, were able to infiltrate the caecum, showing different levels of redundancy between leucocyte subsets during infection.
Bell
L V
LV
Michael Smith building, University of Manchester, Oxford Road, Manchester, UK. louise.bell@manchester.ac.uk
Else
K J
KJ
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002432:Cecum / Q000276:immunology / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D039041:Integrin alpha4beta1 / Q000276:immunology; D016023:Integrins / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D018793:Interleukin-13 / Q000096:biosynthesis; D007420:Intestine, Large / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009088:Mucoproteins; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014257:Trichuriasis / Q000276:immunology*
D015815:Cell Adhesion Molecules; D039041:Integrin alpha4beta1; D016023:Integrins; D018793:Interleukin-13; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; C071777:integrin alpha4beta7; D007371:Interferon-gamma