Open AccessIL-22 Restrains Tapeworm-Mediated Protection against Experimental Colitis via Regulation of IL-25 Expression
Author(s) -
José L. Reyes,
Maria Fernando,
Fernando Lopes,
Gabriella Leung,
Nicole L. Mancini,
Chelsea E. Matisz,
Arthur Wang,
Derek M. McKay
Publication year - 2016
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1005481
Subject(s) - colitis , immune system , hymenolepis diminuta , immunology , mesenteric lymph nodes , cytokine , biology , tumor necrosis factor alpha , microbiology and biotechnology , chemistry , helminths , cestoda
Interleukin (IL)-22, an immune cell-derived cytokine whose receptor expression is restricted to non-immune cells (e.g. epithelial cells), can be anti-inflammatory and pro-inflammatory. Mice infected with the tapeworm Hymenolepis diminuta are protected from dinitrobenzene sulphonic acid (DNBS)-induced colitis. Here we assessed expulsion of H . diminuta , the concomitant immune response and the outcome of DNBS-induced colitis in wild-type (WT) and IL-22 deficient mice (IL-22 -/- ) ± infection. Interleukin-22 -/- mice had a mildly impaired ability to expel the worm and this correlated with reduced or delayed induction of TH2 immunity as measured by splenic and mesenteric lymph node production of IL-4, IL-5 and IL-13 and intestinal Muc-2 mRNA and goblet cell hyperplasia; in contrast, IL-25 increased in the small intestine of IL-22 -/- mice 8 and 12 days post-infection compared to WT mice. In vitro experiments revealed that H . diminuta directly evoked epithelial production of IL-25 that was inhibited by recombinant IL-22. Also, IL-10 and markers of regulatory T cells were increased in IL-22 -/- mice that displayed less DNBS (3 mg, ir. 72h)-induced colitis. Wild-type mice infected with H . diminuta were protected from colitis, as were infected IL-22 -/- mice and the latter to a degree that they were almost indistinguishable from control, non-DNBS treated mice. Finally, treatment with anti-IL-25 antibodies exaggerated DNBS-induced colitis in IL-22 -/- mice and blocked the anti-colitic effect of infection with H . diminuta . Thus, IL-22 is identified as an endogenous brake on helminth-elicited TH2 immunity, reducing the efficacy of expulsion of H . diminuta and limiting the effectiveness of the anti-colitic events mobilized following infection with H . diminuta in a non-permissive host.