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

The Journal of Immunology : Official Journal of the American Association of Immunologists
Umang JainAndrew W Stadnyk

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 (P(KO)) 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 P(KO) mice. Then, using in vitro and in vivo approaches, we show that the mechanism behind the exacerbated inflammation of P(KO) 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 ...Continue Reading

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Citations

Jun 16, 2015·Frontiers in Immunology·Nicolas S MerleLubka T Roumenina
May 28, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Victoria JefferyAnastasia Sobolewski
Oct 27, 2016·Immunological Reviews·Adam Z BlattViviana P Ferreira
Aug 25, 2018·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Marloes A H M MichelsLambertus P W J van den Heuvel
Oct 13, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marloes A H M MichelsUNKNOWN COMBAT Consortium

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