Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - WSX-1
T2 - a key role in induction of chronic intestinal nematode infection
AU - Bancroft, Allison J.
AU - Humphreys, Neil E.
AU - Worthington, John J.
AU - Yoshida, Hiroki
AU - Grencis, Richard K.
PY - 2004/6/15
Y1 - 2004/6/15
N2 - 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.
AB - 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.
KW - Animals
KW - Cecum
KW - Chronic Disease
KW - Gene Expression Regulation
KW - Interferon-gamma
KW - Interleukin-12
KW - Intestinal Diseases, Parasitic
KW - Lymphocyte Count
KW - Mice
KW - Mice, Knockout
KW - Nematode Infections
KW - Receptors, Cytokine
KW - Signal Transduction
KW - Th1 Cells
KW - Trichuriasis
U2 - 10.4049/jimmunol.172.12.7635
DO - 10.4049/jimmunol.172.12.7635
M3 - Journal article
C2 - 15187144
VL - 172
SP - 7635
EP - 7641
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 12
ER -