title: Redundant and pathogenic roles for IL-22 in mycobacterial, protozoan, and helminth infections.
abstract: IL-22 is a member of the IL-10 cytokine family and signals through a heterodimeric receptor composed of the common IL-10R2 subunit and the IL-22R subunit. IL-10 and IL-22 both activate the STAT3 signaling pathway; however, in contrast to IL-10, relatively little is known about IL-22 in the host response to infection. In this study, using IL-22(-/-) mice, neutralizing Abs to IL-22, or both, we show that IL-22 is dispensable for the development of immunity to the opportunistic pathogens Toxoplasma gondii and Mycobacterium avium when administered via the i.p. or i.v. route, respectively. IL-22 also played little to no role in aerosol infections with Mycobacterium tuberculosis and in granuloma formation and hepatic fibrosis following chronic percutaneous infections with the helminth parasite Schistosoma mansoni. A marked pathogenic role for IL-22 was, however, identified in toxoplasmosis when infections were established by the natural oral route. Anti-IL-22 Ab-treated mice developed significantly less intestinal pathology than control Ab-treated mice even though both groups displayed similar parasite burdens. The decreased gut pathology was associated with reduced IL-17A, IL-17F, TNF-alpha, and IFN-gamma expression. In contrast to the prior observations of IL-22 protective effects in the gut, these distinct findings with oral T. gondii infection demonstrate that IL-22 also has the potential to contribute to pathogenic inflammation in the intestine. The IL-22 pathway has emerged as a possible target for control of inflammation in certain autoimmune diseases. Our findings suggest that few if any infectious complications would be expected with the suppression of IL-22 signaling.
authors.affiliation: Immunopathogensis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Wilson
authors.forename: Carl G
authors.initials: CG
authors.lastname: Feng
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Barber
authors.forename: Felix
authors.initials: F
authors.lastname: Yarovinsky
authors.forename: Allen W
authors.initials: AW
authors.lastname: Cheever
authors.forename: Alan
authors.initials: A
authors.lastname: Sher
authors.forename: Michael
authors.initials: M
authors.lastname: Grigg
authors.forename: Mary
authors.initials: M
authors.lastname: Collins
authors.forename: Lynette
authors.initials: L
authors.lastname: Fouser
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Wynn
mesh_terms: D000818:Animals; D020022:Genetic Predisposition to Disease; D018836:Inflammation Mediators / Q000502:physiology; D007378:Interleukins / Q000172:deficiency / Q000502:physiology*; D007411:Intestinal Diseases, Parasitic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008109:Liver Diseases, Parasitic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008581:Meningitis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015270:Mycobacterium avium-intracellulare Infection / Q000235:genetics / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000235:genetics / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000235:genetics / Q000276:immunology*; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology; D000097043:Interleukin-22
chemical_list: D018836:Inflammation Mediators; D007378:Interleukins; D000097043:Interleukin-22