title: IL-22 signaling contributes to West Nile encephalitis pathogenesis.
abstract: 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.
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA. penghua.wang@yale.edu
authors.forename: Penghua
authors.initials: P
authors.lastname: Wang
authors.forename: Fengwei
authors.initials: F
authors.lastname: Bai
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Zenewicz
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Dai
authors.forename: David
authors.initials: D
authors.lastname: Gate
authors.forename: Gong
authors.initials: G
authors.lastname: Cheng
authors.forename: Long
authors.initials: L
authors.lastname: Yang
authors.forename: Feng
authors.initials: F
authors.lastname: Qian
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Yuan
authors.forename: Ruth R
authors.initials: RR
authors.lastname: Montgomery
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Terrence
authors.initials: T
authors.lastname: Town
authors.forename: Erol
authors.initials: E
authors.lastname: Fikrig
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000473:pathology / Q000821:virology; D002465:Cell Movement / Q000276:immunology; D060467:Disease Resistance / Q000276:immunology; D006801:Humans; D007378:Interleukins / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology; D010641:Phenotype; D015398:Signal Transduction / Q000276:immunology*; D053586:Virus Internalization; D014901:West Nile Fever / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D014902:West Nile virus / Q000276:immunology*; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D000097043:Interleukin-22