Properdin provides protection from Citrobacter rodentium-induced intestinal inflammation in a C5a/IL-6-dependent manner

Jain, Umang, Cao, Qi, Thomas, Nikhil A, Woodruff, Trent M, Schwaeble, Wilhelm J, Stover, Cordula M and Stadnyk, Andrew W (2015) Properdin provides protection from Citrobacter rodentium-induced intestinal inflammation in a C5a/IL-6-dependent manner. Journal of Immunology, 194 7: 3414-3421. doi:10.4049/jimmunol.1401814


Author Jain, Umang
Cao, Qi
Thomas, Nikhil A
Woodruff, Trent M
Schwaeble, Wilhelm J
Stover, Cordula M
Stadnyk, Andrew W
Title Properdin provides protection from Citrobacter rodentium-induced intestinal inflammation in a C5a/IL-6-dependent manner
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 1550-6606
0022-1767
Publication date 2015-04-01
Year available 2015
Sub-type Article (original research)
DOI 10.4049/jimmunol.1401814
Open Access Status DOI
Volume 194
Issue 7
Start page 3414
End page 3421
Total pages 8
Place of publication Bethesda, United States
Publisher American Association of Immunologists
Collection year 2016
Language eng
Formatted abstract
Citrobacter rodentium is an attaching and effacing mouse pathogen that models enteropathogenic and enterohemorrhagic Escherichia coli in humans. The complement system is an important innate defense mechanism; however, only scant information is available about the role of complement proteins during enteric infections. In this study, we examined the impact of the lack of properdin, a positive regulator of complement, in C. rodentium–induced colitis. Following infection, properdin knockout (PKO) mice had increased diarrhea and exacerbated inflammation combined with defective epithelial cell–derived IL-6 and greater numbers of colonizing bacteria. The defect in the mucosal response was reversed by administering exogenous properdin to PKO mice. Then, using in vitro and in vivo approaches, we show that the mechanism behind the exacerbated inflammation of PKO mice is due to a failure to increase local C5a levels. We show that C5a directly stimulates IL-6 production from colonic epithelial cells and that inhibiting C5a in infected wild-type mice resulted in defective epithelial IL-6 production and exacerbated inflammation. These outcomes position properdin early in the response to an infectious challenge in the colon, leading to complement activation and C5a, which in turn provides protection through IL-6 expression by the epithelium. Our results unveil a previously unappreciated mechanism of intestinal homeostasis involving complement, C5a, and IL-6 during bacteria-triggered epithelial injury.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Biomedical Sciences Publications
 
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