Colitogenic Bacteroides thetaiotaomicron antigens access host immune cells in a sulfatase-dependent manner via outer membrane vesicles

Christina A. Hickey, Kristine A. Kuhn, David L. Donermeyer, Nathan T. Porter, Chunsheng Jin, Elizabeth A. Cameron, Haerin Jung, Gerard E. Kaiko, Marta Wegorzewska, Nicole P. Malvin, Robert W.P. Glowacki, Gunnar C. Hansson, Paul M. Allen, Eric C. Martens, Thaddeus S. Stappenbeck

Research output: Contribution to journalArticlepeer-review

136 Scopus citations

Abstract

Microbes interact with the host immune system via several potential mechanisms. One essential step for each mechanism is the method by which intestinal microbes or their antigens access specific host immune cells. Using genetically susceptible mice (dnKO) that develop spontaneous, fulminant colitis, triggered by Bacteroides thetaiotaomicron (B. theta), we investigated the mechanism of intestinal microbial access under conditions that stimulate colonic inflammation. B. theta antigens localized to host immune cells through outer membrane vesicles (OMVs) that harbor bacterial sulfatase activity. We deleted the anaerobic sulfatase maturating enzyme (anSME) from B. theta, which is required for post-translational activation of all B. theta sulfatase enzymes. This bacterial mutant strain did not stimulate colitis in dnKO mice. Lastly, access of B. theta OMVs to host immune cells was sulfatase dependent. These data demonstrate that bacterial OMVs and associated enzymes promote inflammatory immune stimulation in genetically susceptible hosts.

Original languageEnglish
Pages (from-to)672-680
Number of pages9
JournalCell Host and Microbe
Volume17
Issue number5
DOIs
StatePublished - May 13 2015

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