WSX-1: a key role in induction of chronic intestinal nematode infection.
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.
Bancroft
Allison J
AJ
School of Biological Sciences, 3.239 Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, United Kingdom. allison.j.bancroft@man.ac.uk
Humphreys
Neil E
NE
Worthington
John J
JJ
Yoshida
Hiroki
H
Grencis
Richard K
RK
D000818:Animals; D002432:Cecum / Q000378:metabolism / Q000469:parasitology; D002908:Chronic Disease; D005786:Gene Expression Regulation / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000494:pharmacology; D007411:Intestinal Diseases, Parasitic / Q000276:immunology*; D018655:Lymphocyte Count; D051379:Mice; D018345:Mice, Knockout; D009349:Nematode Infections / Q000276:immunology; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018123:Receptors, Interleukin; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology; D014257:Trichuriasis / Q000276:immunology*
C484747:Il27ra protein, mouse; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D018664:Interleukin-12; D007371:Interferon-gamma