Redundant and pathogenic roles for IL-22 in mycobacterial, protozoan, and helminth infections

Mark S. Wilson, Carl G. Feng, Daniel L. Barber, Felix Yarovinsky, Allen W. Cheever, Alan Sher, Michael Grigg, Mary Collins, Lynette Fouser, Thomas A. Wynn

Research output: Contribution to journalArticle

99 Scopus citations

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-α, and IFN-γ 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.

Original languageEnglish (US)
Pages (from-to)4378-4390
Number of pages13
JournalJournal of Immunology
Volume184
Issue number8
DOIs
StatePublished - Apr 15 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Wilson, M. S., Feng, C. G., Barber, D. L., Yarovinsky, F., Cheever, A. W., Sher, A., Grigg, M., Collins, M., Fouser, L., & Wynn, T. A. (2010). Redundant and pathogenic roles for IL-22 in mycobacterial, protozoan, and helminth infections. Journal of Immunology, 184(8), 4378-4390. https://doi.org/10.4049/jimmunol.0903416