Interaction of Gut Cells with Bacterial Outer Membrane Vesicles Triggers Inflammatory Bowel Disease in Mouse Model

These moieties may be found on a range of substrates, including steroids, carbohydrates and proteins. Sulfatases play important roles in the cycling of sulfur in the environment, in the degradation of sulfated glycosaminoglycans and glycolipids in the lysosome, and in remodeling sulfated glycosaminoglycans in the extracellular space.

Investigators at the Washington University School of Medicine (St. Louis, MO, USA) worked with a genetically engineered mouse model (dnKO) that developed spontaneous, fulminant colitis when triggered by the Gram-negative, obligatory anaerobic bacterium Bacteroides thetaiotaomicron.

Results published in the May 13, 2015, issue of the journal Cell Host & Microbe revealed that B. thetaiotaomicron antigens localized to host immune cells through outer membrane vesicles (OMVs) that harbored bacterial sulfatase activity. Access of B. thetaiotaomicron OMVs to host immune cells was sulfatase dependent.

OMVs are a means for bacteria to communicate among themselves and with other living forms in their environment via nanoscale membrane vesicles in their outer membranes. These vesicles are involved in trafficking bacterial cell signaling biochemicals, which may include DNA, RNA, proteins, endotoxins, and allied virulence molecules.

The investigators deleted the anaerobic sulfatase maturating enzyme (anSME), which is required for post-translational activation of all sulfatase enzymes, from B. thetaiotaomicron. This bacterial mutant strain did not stimulate colitis in dnKO mice.

"The immune cells do not need to encounter the bacteria to cause inflammation—all they need to do is encounter the vesicles," said senior author Dr. Thad Stappenbeck, professor of pathology and immunology at the Washington University School of Medicine. "We did not realize that was possible, and we think this discovery could change our thinking about not just IBD but other autoimmune disorders and infectious diseases."

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