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Mucosal Immunol. 2018 Jul;11(4):1181-1190. doi: 10.1038/s41385-018-0005-8. Epub 2018 May 4.

Interleukin-22-deficiency and microbiota contribute to the exacerbation of Toxoplasma gondii-induced intestinal inflammation.

Author information

1
Laboratory of Experimental and Molecular Immunology and Neurogenetics (INEM), CNRS and University of Orleans (UMR7355), Orléans, France.
2
CNRS UPS44 -TAAM, Orléans, France.
3
Sorbonne Universités, UPMC Univ. Paris 06, École Normale Supérieure, PSL Research University, CNRS, INSERM, APHP, Laboratoire des Biomolécules (LBM), 27 rue de Chaligny, 75005, Paris, France.
4
Ludwig Institute for Cancer Research, Université Catholique de Louvain, Brussels, Belgium.
5
INSERM U1068, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix-Marseille Université and Institut Paoli-Calmette, Parc Scientifique et Technologique de Luminy, CNRS UMR 7258, Marseille, France.
6
Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, 20246, Germany.
7
L'Institut de Pasteur, Lille, France.
8
Micalis Institute, Institut National de la Recherche Agronomique (INRA), AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, 78352, France.
9
Department of Gastroenterology, Saint Antoine Hospital, Assistance Publique-Hopitaux de Paris, UPMC, Paris, France.
10
Laboratory of Experimental and Molecular Immunology and Neurogenetics (INEM), CNRS and University of Orleans (UMR7355), Orléans, France. bryffel@cnrs-orleans.fr.

Abstract

Upon oral infection with Toxoplasma gondii cysts (76 K strain) tachyzoites are released into the intestinal lumen and cross the epithelial barrier causing damage and acute intestinal inflammation in C57BL/6 (B6) mice. Here we investigated the role of microbiota and IL-22 in T.gondii-induced small intestinal inflammation. Oral T.gondii infection in B6 mice causes inflammation with IFNγ and IL-22 production. In IL-22-deficient mice, T.gondii infection augments the Th1 driven inflammation. Deficiency in either IL-22bp, the soluble IL-22 receptor or Reg3γ, an IL-22-dependent antimicrobial lectin/peptide, did not reduce inflammation. Under germ-free conditions, T.gondii-induced inflammation was reduced in correlation with parasite load. But intestinal inflammation is still present in germ-free mice, at low level, in the lamina propria, independently of IL-22 expression. Exacerbated intestinal inflammation driven by absence of IL-22 appears to be independent of IL-22 deficiency associated-dysbiosis as similar inflammation was observed after fecal transplantation of IL-22-/- or WT microbiota to germ-free-WT mice. Our results suggest cooperation between parasite and intestinal microbiota in small intestine inflammation development and endogenous IL-22 seems to exert a protective role independently of its effect on the microbiota. In conclusion, IL-22 participates in T.gondii induced acute small intestinal inflammation independently of microbiota and Reg3γ.

PMID:
29728643
DOI:
10.1038/s41385-018-0005-8
[Indexed for MEDLINE]

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