Redundant and pathogenic roles for IL-22 in mycobacterial, protozoan, and helminth infections.
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.
Wilson
Mark S
MS
Immunopathogensis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Feng
Carl G
CG
Barber
Daniel L
DL
Yarovinsky
Felix
F
Cheever
Allen W
AW
Sher
Alan
A
Grigg
Michael
M
Collins
Mary
M
Fouser
Lynette
L
Wynn
Thomas A
TA
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
D018836:Inflammation Mediators; D007378:Interleukins; D000097043:Interleukin-22