title: Attenuation of intestinal inflammation in interleukin-10-deficient mice infected with Citrobacter rodentium.
abstract: Interleukin-10 (IL-10) curtails immune responses to microbial infection and autoantigens and contributes to intestinal immune homeostasis, yet administration of IL-10 has not been effective at attenuating chronic intestinal inflammatory conditions, suggesting that its immune functions may be context dependent. To gain a broader understanding of the importance of IL-10 in controlling mucosal immune responses to infectious challenges, we employed the murine attaching and effacing pathogen Citrobacter rodentium, which colonizes primarily the surfaces of the cecum and colon and causes transient mucosal inflammation driven by Th17 and Th1 T helper cells. Infection induced macrophage and dendritic cell production of IL-10, which diminished antibacterial host defenses, because IL-10-deficient mice cleared infection faster than wild-type controls. In parallel, the mice had less acute infection-associated colitis and resolved it more rapidly than controls. Importantly, transient C. rodentium infection protected IL-10-deficient mice against the later development of spontaneous colitis that normally occurs with aging in these mice. Genome-wide expression studies revealed that IL-10 deficiency was associated with downregulation of proinflammatory pathways but increased expression of the anti-inflammatory cytokine IL-27 in response to infection. IL-27 was found to suppress in vitro Th17 and, to a lesser degree, Th1 differentiation independent of IL-10. Furthermore, neutralization of IL-27 resulted in more severe colitis in infected IL-10-deficient mice. Together, these findings indicate that IL-10 is dispensable for resolving C. rodentium-associated colitis and further suggest that IL-27 may be a critical factor for controlling intestinal inflammation and Th17 and Th1 development by IL-10-independent mechanisms.
authors.affiliation: Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Dann
authors.forename: Christine
authors.initials: C
authors.lastname: Le
authors.forename: Barun K
authors.initials: BK
authors.lastname: Choudhury
authors.forename: Houpu
authors.initials: H
authors.lastname: Liu
authors.forename: Omar
authors.initials: O
authors.lastname: Saldarriaga
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Hanson
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Cong
authors.forename: Lars
authors.initials: L
authors.lastname: Eckmann
mesh_terms: D000375:Aging; D000818:Animals; D044082:Citrobacter rodentium; D004756:Enterobacteriaceae Infections / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D007249:Inflammation / Q000382:microbiology*; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: C486767:Il27 protein, mouse; D007378:Interleukins; D016753:Interleukin-10