Group A streptococci have earned the popular name 'flesh-eating bacteria' for their role in an often fatal infection of soft tissues, necrotizing fasciitis. But the same type of bacteria can also cause only mild illness, such as strep throat. Why do some people walk away unscathed from Strep A infection while others succumb to horrible disease? In the December issue of Nature Medicine, Malak Kotb at the Veterans Affairs Medical Center in Memphis and colleagues begin to answer the question. They had an inkling that a particular set of genes might have something to do with susceptibility to infection. These genes, called HLA-II genes, encode proteins on the cell surface of immune cells. It’s known that these proteins can bind to certain toxins secreted by Strep A.
The authors examined the HLA-II genes from 279 individuals afflicted with severe infection – either necrotizing fasciitis or streptococcal toxic shock syndrome – and compared them to the HLA-II genes of 256 healthy individuals. Certain HLA-II gene variants were present more often in individuals with severe infection, while other variants were present more frequently in healthy individuals. The authors also found that immune cells with either predisposing or protective HLA-II gene variants differed in their response to bacterial toxins. There are numerous previous reports of association between HLA variants and diseases such as multiple sclerosis, arthritis, and type 1 diabetes. This study, however, delves into the mechanism, and also presents an opportunity for further study in mice – mice can be engineered to express human HLA genes, and are also susceptible to infection by group A streptococci.
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