Chronic Exposure to Bacterial Superantigens Induces Diabetes-Like Symptoms in Rabbit Model

aureus superantigen toxic shock syndrome toxin-1 (TSST-1).

Superantigens (SAgs) are a class of antigens which cause nonspecific activation of T-cells resulting in polyclonal T-cell activation and massive cytokine release. SAgs can be produced by pathogenic microbes (including viruses, mycoplasma, and bacteria) as a defense mechanism against the immune system. Compared to a normal antigen-induced T-cell response where 0.01%–0.1% of the body’s T-cells are activated, these SAgs are capable of activating up to 25% of the body’s T-cells. The large number of activated T-cells generates a massive immune response which is not specific to any particular epitope on the SAg, thus undermining one of the fundamental strengths of the adaptive immune system, that is, its ability to target antigens with high specificity.

The investigators reported in the February 24, 2015, online edition of the journal mBio that rabbits experiencing chronic exposure to the S. aureus toxin developed impaired glucose tolerance, systemic inflammation, and elevated endotoxin levels in the bloodstream, all of which are common characteristics of type II diabetes. Additional experiments showed that cultures of fat cells (adipocytes) exposed to the toxin developed diabetes type II-like glucose intolerance.

"We basically reproduced Type II diabetes in rabbits simply through chronic exposure to the staph superantigen," said senior author Dr. Patrick Schlievert, professor of microbiology at the University of Iowa. "What we are finding is that as people gain weight, they are increasingly likely to be colonized by staph bacteria—to have large numbers of these bacteria living on the surface of their skin. People who are colonized by staph bacteria are being chronically exposed to the superantigens the bacteria are producing."

"I think we have a way to intercede here and alter the course of diabetes," said Dr. Schlievert. "We are working on a vaccine against the superantigens and we believe that this type of vaccine could prevent the development of type II diabetes."

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University of Iowa