TY - JOUR
T1 - Colitogenic Bacteroides thetaiotaomicron antigens access host immune cells in a sulfatase-dependent manner via outer membrane vesicles
AU - Hickey, Christina A.
AU - Kuhn, Kristine A.
AU - Donermeyer, David L.
AU - Porter, Nathan T.
AU - Jin, Chunsheng
AU - Cameron, Elizabeth A.
AU - Jung, Haerin
AU - Kaiko, Gerard E.
AU - Wegorzewska, Marta
AU - Malvin, Nicole P.
AU - Glowacki, Robert W.P.
AU - Hansson, Gunnar C.
AU - Allen, Paul M.
AU - Martens, Eric C.
AU - Stappenbeck, Thaddeus S.
N1 - Funding Information:
C.A.H. is a Fellow of the Pediatric Scientist Development Program. This work was supported by award number K12-HD000850 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (C.A.H.) and by DK097079 (P.M.A., E.C.M., and T.S.S.). We thank D. Kreamalmeyer for animal care and breeding, W. Beatty for electron microscopy, C. Lai for graphical art, and Herbert W. Virgin and Emil R. Unanue for insights on the manuscript. Experimental support was provided by the Digestive Disease Research Core Center (NIH award number P30DK052574) of Washington University. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The data reported in this paper are tabulated in the Supplemental Information .
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/5/13
Y1 - 2015/5/13
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84929298167&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2015.04.002
DO - 10.1016/j.chom.2015.04.002
M3 - Article
C2 - 25974305
AN - SCOPUS:84929298167
VL - 17
SP - 672
EP - 680
JO - Cell Host and Microbe
JF - Cell Host and Microbe
SN - 1931-3128
IS - 5
ER -