title: IL-22 is mainly produced by IFNγ-secreting cells but is dispensable for host protection against Mycobacterium tuberculosis infection.
abstract: Anti-inflammatory treatment of autoimmune diseases is associated with an increased risk of reactivation tuberculosis (TB). Besides interleukin (IL-17)A, IL-22 represents a classical T helper (TH)17 cytokine and shares similar pathological effects in inflammatory diseases such as psoriasis or arthritis. Whereas IL-17A supports protective immune responses during mycobacterial infections, the role of IL-22 after infection with Mycobacterium tuberculosis (Mtb) is yet poorly characterized. Therefore, we here characterize the cell types producing IL-22 and the protective function of this cytokine during experimental TB in mice. Like IL-17A, IL-22 is expressed early after infection with Mtb in an IL-23-dependent manner. Surprisingly, the majority of IL-22-producing cells are not positive for IL-17A but have rather functional characteristics of interferon-gamma-producing TH1 cells. Although we found minor differences in the number of naive and central memory T cells as well as in the frequency of TH1 and polyfunctional T cells in mice deficient for IL-22, the absence of IL-22 does not affect the outcome of Mtb infection. Our study revealed that although produced by TH1 cells, IL-22 is dispensable for protective immune responses during TB. Therefore, targeting of IL-22 in inflammatory disease may represent a therapeutic approach that does not incur the danger of reactivation TB.
authors: Infection Immunology, Research Center Borstel (RCB), Borstel, Germany.
authors: Jochen
authors: J
authors: Behrends
authors: Jean-Christophe
authors: JC
authors: Renauld
authors: Stefan
authors: S
authors: Ehlers
authors: Christoph
authors: C
authors: Hölscher
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D006098:Granulocytes / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000276:immunology*; D007109:Immunity / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism*; D053759:Interleukin-23 / Q000378:metabolism; D007378:Interleukins / Q000096:biosynthesis* / Q000172:deficiency; D008213:Lymphocyte Activation / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D000097043:Interleukin-22
chemical_list: D000942:Antigens, Bacterial; D018836:Inflammation Mediators; D007371:Interferon-gamma; D053759:Interleukin-23; D007378:Interleukins; D000097043:Interleukin-22