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Campylobacter jejuni disrupts protective Toll-like receptor 9 signaling in colonic epithelial cells and increases the severity of dextran sulfate sodium-induced colitis in mice.
Infect Immun 2012; 80(4):1563-71II

Abstract

Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation associated with a dysregulated immune response to commensal bacteria in susceptible individuals. The relapse of IBD may occur following an infection with Campylobacter jejuni. Apical epithelial Toll-like receptor 9 (TLR9) activation by bacterial DNA is reported to maintain colonic homeostasis. We investigated whether a prior C. jejuni infection disrupts epithelial TLR9 signaling and increases the severity of disease in a model of mild dextran sulfate sodium (DSS) colitis in mice. In a further attempt to identify mechanisms, T84 monolayers were treated with C. jejuni followed by a TLR9 agonist. Transepithelial resistance (TER) and dextran flux across confluent monolayers were monitored. Immunohistochemistry, Western blotting, and flow cytometry were used to examine TLR9 expression. Mice colonized by C. jejuni lacked any detectable pathology; however, in response to low levels of DSS, mice previously exposed to C. jejuni exhibited significantly reduced weight gain and increased occult blood and histological damage scores. Infected mice treated with DSS also demonstrated a significant reduction in levels of the anti-inflammatory cytokine interleukin-25. In vitro studies indicated that apical application of a TLR9 agonist enhances intestinal epithelial barrier function and that this response is lost in C. jejuni-infected monolayers. Furthermore, infected cells secreted significantly more CXCL8 following the basolateral application of a TLR9 agonist. Surface TLR9 expression was reduced in C. jejuni-infected monolayers subsequently exposed to a TLR9 agonist. In conclusion, infection by C. jejuni disrupts TLR9-induced reinforcement of the intestinal epithelial barrier, and colonization by C. jejuni increases the severity of mild DSS colitis.

Authors+Show Affiliations

Department of Biological Sciences and Inflammation Research Network, University of Calgary, Calgary, Alberta, Canada.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22311925

Citation

O'Hara, Jennifer R., et al. "Campylobacter Jejuni Disrupts Protective Toll-like Receptor 9 Signaling in Colonic Epithelial Cells and Increases the Severity of Dextran Sulfate Sodium-induced Colitis in Mice." Infection and Immunity, vol. 80, no. 4, 2012, pp. 1563-71.
O'Hara JR, Feener TD, Fischer CD, et al. Campylobacter jejuni disrupts protective Toll-like receptor 9 signaling in colonic epithelial cells and increases the severity of dextran sulfate sodium-induced colitis in mice. Infect Immun. 2012;80(4):1563-71.
O'Hara, J. R., Feener, T. D., Fischer, C. D., & Buret, A. G. (2012). Campylobacter jejuni disrupts protective Toll-like receptor 9 signaling in colonic epithelial cells and increases the severity of dextran sulfate sodium-induced colitis in mice. Infection and Immunity, 80(4), pp. 1563-71. doi:10.1128/IAI.06066-11.
O'Hara JR, et al. Campylobacter Jejuni Disrupts Protective Toll-like Receptor 9 Signaling in Colonic Epithelial Cells and Increases the Severity of Dextran Sulfate Sodium-induced Colitis in Mice. Infect Immun. 2012;80(4):1563-71. PubMed PMID: 22311925.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Campylobacter jejuni disrupts protective Toll-like receptor 9 signaling in colonic epithelial cells and increases the severity of dextran sulfate sodium-induced colitis in mice. AU - O'Hara,Jennifer R, AU - Feener,Troy D, AU - Fischer,Carrie D, AU - Buret,Andre G, Y1 - 2012/02/06/ PY - 2012/2/8/entrez PY - 2012/2/9/pubmed PY - 2012/5/11/medline SP - 1563 EP - 71 JF - Infection and immunity JO - Infect. Immun. VL - 80 IS - 4 N2 - Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation associated with a dysregulated immune response to commensal bacteria in susceptible individuals. The relapse of IBD may occur following an infection with Campylobacter jejuni. Apical epithelial Toll-like receptor 9 (TLR9) activation by bacterial DNA is reported to maintain colonic homeostasis. We investigated whether a prior C. jejuni infection disrupts epithelial TLR9 signaling and increases the severity of disease in a model of mild dextran sulfate sodium (DSS) colitis in mice. In a further attempt to identify mechanisms, T84 monolayers were treated with C. jejuni followed by a TLR9 agonist. Transepithelial resistance (TER) and dextran flux across confluent monolayers were monitored. Immunohistochemistry, Western blotting, and flow cytometry were used to examine TLR9 expression. Mice colonized by C. jejuni lacked any detectable pathology; however, in response to low levels of DSS, mice previously exposed to C. jejuni exhibited significantly reduced weight gain and increased occult blood and histological damage scores. Infected mice treated with DSS also demonstrated a significant reduction in levels of the anti-inflammatory cytokine interleukin-25. In vitro studies indicated that apical application of a TLR9 agonist enhances intestinal epithelial barrier function and that this response is lost in C. jejuni-infected monolayers. Furthermore, infected cells secreted significantly more CXCL8 following the basolateral application of a TLR9 agonist. Surface TLR9 expression was reduced in C. jejuni-infected monolayers subsequently exposed to a TLR9 agonist. In conclusion, infection by C. jejuni disrupts TLR9-induced reinforcement of the intestinal epithelial barrier, and colonization by C. jejuni increases the severity of mild DSS colitis. SN - 1098-5522 UR - https://www.unboundmedicine.com/medline/citation/22311925/Campylobacter_jejuni_disrupts_protective_Toll_like_receptor_9_signaling_in_colonic_epithelial_cells_and_increases_the_severity_of_dextran_sulfate_sodium_induced_colitis_in_mice_ L2 - http://iai.asm.org/cgi/pmidlookup?view=long&pmid=22311925 DB - PRIME DP - Unbound Medicine ER -