A white blood cell interacts with the MRSA bacterium (yellow). | Flickr/ NIAID/ CC BY 2.0
A key skin protein previously overlooked in studies of staph infection has the ability to quell antibiotic-resistant staph- and strep-based skin infections, according to a study in the 18 November issue of Science Immunology.
Warren J. Leonard, an investigator at the NIH National Heart, Lung and Blood Institute, said that channeling the protein’s effects could lead to potential therapeutic routes for detrimental and prevalent skin infections, such as methicillin-resistant Staphylococcus aureus, or MRSA.
MRSA is a stubborn and persistent bacterium that “has been reported as the most common cause of skin and soft-tissue infections among emergency room patients in 11 U.S. cities,” said Leonard. Although the bacterium normally causes a skin infection, MRSA can be fatal when it leads to more invasive infections, such as pneumonia, sepsis and meningitis — causing more deaths in the U.S. than HIV, viral hepatitis and tuberculosis combined.
To help formulate effective therapies against MRSA, researchers need a better understanding of how the immune system can combat unyielding bacteria. This need led Leonard and his colleagues to investigate components of the body’s infection-combating defenses that may have been overlooked in the past.
They noted that a protein called thymic stromal lymphopoietin (TSLP) had not been explored in the context of MRSA and other skin infections before, despite the fact that it is highly active on the skin. Previous studies have primarily concentrated on TSLP’s more established roles in allergic diseases, such as asthma and atopic dermatitis, which may have overshadowed its possible connections to other types of infection.
While “some studies have examined the role of TSLP related to infection, we focused on skin infections,” noted Leonard.
In human donor cells and mouse experimental models, the researchers demonstrated that TSLP specifically targeted neutrophils — white blood cells that constitute the first line of defense against bacterial infections.
“Our study indicates that TSLP promotes the killing of MRSA by neutrophils in mouse models of skin infections, and thus can help lower the number of MRSA bacteria,” said Leonard. Other types of bacteria that cause skin infection, such as Streptococcus pyogenes, were also found in lower quantities in the infected mice after they were treated with TSLP.
By contrast, “the absence of TSLP signaling in mouse control groups resulted in a higher number of MRSA bacteria,” said Leonard, who noted that there were similar results in human cells.
Leonard and his team’s findings add to the developing hypothesis that immune responses can vary drastically depending on the organ. In this case, TSLP provides an antibacterial function on the skin, while in previous studies it was shown to promote disease in other organs like the gut. The researchers are now working to “better understand the underlying mechanisms of TSLP’s antibacterial effects,” said Leonard.