Chlamydia muridarum Alleviates Colitis via the IL-22/Occludin Signal Pathway

Abstract

Ulcerative colitis (UC) is the most common inflammatory bowel disease, and its incidence has increased in recent years. Recent clinical and experimental data indicate that gut microbiota plays a pivotal role in the pathogenesis of UC. Chlamydia establishes a stable and persistent colonization in the gastrointestinal tract without apparent pathogenicity to gastrointestinal or extragastrointestinal tissues. However, the detailed effects of Chlamydia on the gastrointestinal tissue remain unknown. The primary aim of this study is to investigate the effects of Chlamydia muridarum (C. muridarum) on development of colitis induced by dextran sodium sulfate (DSS) and the underlying molecular mechanism. The results suggested that C. muridarum significantly improved colitis symptoms—including weight loss, disease activity index, colon length, and histopathological changes in the colon caused by DSS—and alleviated the reduced expression of interleukin-22 and occludin in the colonic tissue due to DSS administration. Furthermore, the absence of IL-22 completely prevented C. muridarum from alleviating colitis and significantly decreased the levels of occludin, an important downstream effector protein of IL-22. These findings suggest that C. muridarum ameliorates ulcerative colitis induced by DSS via the IL-22/occludin signal pathway.

Chlamydia muridarumCauses Persistent Subclinical Infection and Elicits Innate and Adaptive Immune Responses in C57BL/6J, BALB/cJ and J:ARC(S) Mice Following Exposure to Shedding Mice

“…33 Experimentally, Cm has been shown to promote the expression of both IL-17 and IL-22. 15,62 IL-6 (associated with T-cell survival, downregulation of T regs , and as noted is protective against chlamydial infection) and IL-12 (which functions in tandem with IFNγ) were the principal elevated circulating pro-inflammatory cytokines. 65 We recently reported that mice deficient in IL-12 activity developed fulminant, fatal disease after Cm infection, supporting the important role this cytokine plays in response to infection with Cm.…”

“…These findings are consistent with previous oral experimental infections of Cm. 44,62 This phenotype may be attributable to the formation of non-replicating "aberrant bodies," downregulation of the immune response/development of host tolerance, and/or bacterial survival mechanisms. 44,69 Cm was only detected in epithelia and was generally restricted to epithelium overlying GALT, which became hyperplastic most likely a result of chronic immune stimulation.…”

“…Given that Cm colonizes the gastrointestinal tract and has been demonstrated to primarily elicit a Th1 immune response, we sought to further investigate the large intestinal immune responses of B6 mice following infection with Cm. 62,66 The local responses were much more robust with both greater numbers of immune cells (CD45 + ), myeloid cells (Ly6G + ), and effector (activated) CD4 + T cells in both early and late timepoints of Cm infection. CD4 + T eff were frequently positive for Tbet and RORγ, and produced IFNγ, IL-17A, and IL-22 indicating both a Th1 cell response and Th17 cell activation.…”

Therapeutic Effects of Zymomonas mobilis on Experimental DSS-Induced Colitis Mouse Model

“…The other structural protein studied, Occludin, is a component of intercellular tight junctions which promotes this barrier's structural integrity [46,47]. Its expression is associated with the recovery of the intestinal mucosa.…”