TY - JOUR
T1 - IL-22 Signaling Contributes to West Nile Encephalitis Pathogenesis
AU - Wang, Penghua
AU - Bai, Fengwei
AU - Zenewicz, Lauren A.
AU - Dai, Jianfeng
AU - Gate, David
AU - Cheng, Gong
AU - Yang, Long
AU - Qian, Feng
AU - Yuan, Xiaoling
AU - Montgomery, Ruth R.
AU - Flavell, Richard A.
AU - Town, Terrence
AU - Fikrig, Erol
PY - 2012/8/28
Y1 - 2012/8/28
N2 - The Th17 cytokine, IL-22, regulates host immune responses to extracellular pathogens. Whether IL-22 plays a role in viral infection, however, is poorly understood. We report here that Il22-/- mice were more resistant to lethal West Nile virus (WNV) encephalitis, but had similar viral loads in the periphery compared to wild type (WT) mice. Viral loads, leukocyte infiltrates, proinflammatory cytokines and apoptotic cells in the central nervous system (CNS) of Il22-/- mice were also strikingly reduced. Further examination showed that Cxcr2, a chemokine receptor that plays a non-redundant role in mediating neutrophil migration, was significantly reduced in Il22-/- compared to WT leukocytes. Expression of Cxcr2 ligands, cxcl1 and cxcl5, was lower in Il22-/- brains than wild type mice. Correspondingly, neutrophil migration from the blood into the brain was attenuated following lethal WNV infection of Il22-/- mice. Our results suggest that IL-22 signaling exacerbates lethal WNV encephalitis likely by promoting WNV neuroinvasion.
AB - The Th17 cytokine, IL-22, regulates host immune responses to extracellular pathogens. Whether IL-22 plays a role in viral infection, however, is poorly understood. We report here that Il22-/- mice were more resistant to lethal West Nile virus (WNV) encephalitis, but had similar viral loads in the periphery compared to wild type (WT) mice. Viral loads, leukocyte infiltrates, proinflammatory cytokines and apoptotic cells in the central nervous system (CNS) of Il22-/- mice were also strikingly reduced. Further examination showed that Cxcr2, a chemokine receptor that plays a non-redundant role in mediating neutrophil migration, was significantly reduced in Il22-/- compared to WT leukocytes. Expression of Cxcr2 ligands, cxcl1 and cxcl5, was lower in Il22-/- brains than wild type mice. Correspondingly, neutrophil migration from the blood into the brain was attenuated following lethal WNV infection of Il22-/- mice. Our results suggest that IL-22 signaling exacerbates lethal WNV encephalitis likely by promoting WNV neuroinvasion.
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U2 - 10.1371/journal.pone.0044153
DO - 10.1371/journal.pone.0044153
M3 - Article
C2 - 22952908
AN - SCOPUS:84865483236
SN - 1932-6203
VL - 7
JO - PloS one
JF - PloS one
IS - 8
M1 - e44153
ER -