First Author | Bancroft AJ | Year | 2004 |
Journal | J Immunol | Volume | 172 |
Issue | 12 | Pages | 7635-41 |
PubMed ID | 15187144 | Mgi Jnum | J:90821 |
Mgi Id | MGI:3044836 | Doi | 10.4049/jimmunol.172.12.7635 |
Citation | Bancroft AJ, et al. (2004) WSX-1: a key role in induction of chronic intestinal nematode infection. J Immunol 172(12):7635-41 |
abstractText | Chronic infection by the gastrointestinal nematode Trichuris muris in susceptible AKR mice, which mount a Th1 response, is associated with IL-27p28 expression in the cecum. In contrast to wild-type mice, mice that lack the WSX-1/IL-27R gene fail to harbor a chronic infection, having significantly lower Th1 responses. The lower level of Ag-specific IFN-gamma-positive cells in WSX-1 knockout (KO) mice was found to be CD4(+) T cell specific, and the KO mice also had increased levels of IL-4-positive CD4(+) T cells. Polyclonal activation of mesenteric lymph node cells from naive WSX-1 KO or wild-type mice demonstrated that there was no inherent defect in the production of IFN-gamma by CD4(+) T cells, suggesting the decrease in these cells seen in infected WSX-1 KO mice is an in vivo Ag-driven effect. IL-12 treatment of WSX-1 KO mice failed to rescue the type 1 response, resulting in unaltered type-2-driven resistance. Infection of WSX-1 KO mice was also associated with a reduction of IL-27/WSX-1 downstream signaling gene expression within the cecum. These studies demonstrate an important role for WSX-1 signaling in the promotion of type 1 responses and chronic gastrointestinal nematode infection. |