Mast cells fight bacteria

Key Points

Dr. Di Nardo, assistant professor in the department of medicine-dermatology at the University of California, San Diego, says the findings are encouraging, although the mast cell defense activity was mediated by expression of cathelicidin antimicrobial peptides.

"Mast cell activity is after barrier penetration," she tells Dermatology Times.

Specifically, Dr. Di Nardo says her current research is to "work on the molecular regulators of antimicrobials like toll receptors and interleukins and vitamin D."

Researchers evaluated skin lesions and bacteria in the blood of 15 mice subjects and 15 mice controls. They tested the effect that Group A streptococcus would have on the skin when it was injected and applied to the skin.

Dr. Di Nardo says Group A streptococcus used in the study can lead to infections and resulting illnesses that are, for the most part, relatively mild, such as strep throat and impetigo.

"Occasionally, however, these bacteria can cause much more severe and even life-threatening diseases, such as necrotizing fasciitis (sometimes described as 'the flesh-eating bacteria') and streptococcal toxic shock syndrome." Dr. Di Nardo cites statistics from the U.S. Centers for Disease Control and Prevention that show 500 to 1,500 cases of necrotizing fasciitis and 2,000 to 3,000 cases of streptococcal toxic shock syndrome are reported annually in the United States.

"People may carry Group A streptococci in their throat or on their skin and have no symptoms of disease," Dr. Di Nardo notes.

The researchers set out to test their hypothesis that the presence of mast cells, which express cathelicidins, would influence skin infections. The cathelicidins are peptides that act as antibiotics by killing microbes.

They gave subcutaneous injections of Group A streptococcus to 15 mice that had a mast cell deficiency and compared them with 15 healthy controls. Four days after the streptococcus injections, results showed that skin lesions were 30 percent larger, and there were 80 percent more lesional bacteria in the mast cell-deficient mice than in controls. Treated mice also had 30 percent more bacteria in the blood than controls did.

To determine if these differences in lesions and systemic bacteria between treated mice and controls were due to the presence of the antimicrobial peptide cathelicidin found in mast cells, the researchers reconstituted the skin of the mice who had mast cell deficiencies. To do this, they obtained mast cells from the bone marrow of either wild-type or cathelicidin-deficient mice. Two weeks after mast cell transplantation, the specimens were challenged with Group A streptococcus injections.

Forty-eight hours after injection, the skins were assessed. Results show that the mice who did not receive mast cells had an average lesion size of 250 mm². Mice skin that was reconstituted with wild-type mast cells had normal-sized lesions of 10 mm².

In contrast, mice skin that was reconstituted with cathelicidin-deficient mast cells had lesions measuring 200 mm² . These latter mice also had greater systemic bacteremia, which was evidenced by spleens recovered with an increased bacterial load.

"This means that the mast cells control gram-positive skin invasion through the expression of cathelicidin antimicrobial peptide," Dr. Di Nardo explains.

Another facet of the mice study evaluated the differences in bacterial point of entry: either from the skin surface or subcutaneously by injection. The researchers sought to better define the role of mast cells in controlling bacterial infection. To do this, they grew Group A streptococcus in a bacteria medium and then applied the resulting gel to the skin of the mast cell-deficient mice and also to the controls. After 18 hours, they removed the gel, washed the skin and took samples to measure bacteria.

In this scenario, skins of the two different mice groups (mast-cell-deficient treatment mice and controls) were not significantly different after topical application of the gel containing Group A streptococcus bacteria. This is in contrast to the findings presented above that showed significant differences in skin lesion size and quantity amongst treatment mice and controls after Group A streptococcus was injected.

With this comparison finding, the researchers conclude that "Mast cell activity is after barrier penetration."

Dr. Di Nardo says that because varied lesions resulted after injections but not after topical applications of Group A streptococcus, dermatologists should remember that "Any wound is a good breach for Group A streptococcus infection."