TSLP Induces Neutrophil-mediated Killing of Methicillin-resistant Staphylococcus Aureus (MRSA)

This technology includes the use of thymic stromal lymphopoetin (TSLP) for the treatment of MRSA. Our studies show that mouse neutrophils express the TSLP receptor, TSLPR, and that TSLP protein is increased during cutaneous MRSA infection. Using in vitro MRSA whole blood killing assays, we show that TSLP acts on mouse neutrophils to enhance MRSA killing. In an in vivo MRSA intradermal ear infection, TSLPR-deficient mice exhibit increased MRSA burden compared to wild-type mice. Moreover, TSLP treatment increases cutaneous MRSA killing in wild-type mice, as intradermal TSLP treatment of wild-type mice results in significantly enhanced MRSA killing in the ear. In addition, using TSLPR-deficient mice, we show that the effect of TSLP on MRSA killing is TSLPR dependent. Furthermore, TSLP increases MRSA killing in human whole blood and also acts directly on purified human neutrophils to increase control of MRSA. These data indicate that TSLP acts on both mouse and human neutrophils to increase MRSA killing and may have implications for the treatment of cutaneous MRSA infections.