MedicalResearch.com Interview with:
Warren Leonard, M.D.
NIH Distinguished Investigator
Laboratory of Molecular Immunology
MedicalResearch.com: What is the background for this study?
Response: TSLP is a cytokine that has been well studied in the context of T cell helper type 2 (TH2) responses and the promotion of atopic diseases. TSLP is naturally expressed at barrier surfaces, such as the skin; however, its role in skin infections was not previously explored.
In our study, we investigated whether TSLP plays a role in host defense to Staphylococcus aureus skin infections, using the most common strain of methicillin-resistant S. aureus (MRSA) present in the United States.
MedicalResearch.com: What are the main findings?
Response: We found that TSLP acts directly on both mouse and human neutrophils to enhance neutrophil killing of MRSA. It also enhanced in vivo killing of another strain of S. aureus and Streptococcus pyogenes (another major human skin pathogen).
We also elucidated the mechanism: TSLP augmented neutrophil-mediated killing of MRSA in a manner that depended on reactive oxygen species and activation of the complement system. Our study therefore identified a previously unappreciated link between TSLP and the complement system.
MedicalResearch.com: Do you think there is a role for in TSLP in eczema, especially with regard to the increased susceptibility of atopic patients to Staph infections?
Response: There is an association of genetic variants of TSLP with eczema, and TSLP has been linked to allergic diseases, including atopic dermatitis. It has been shown to play a role in the promotion and progression of atopic dermatitis in mouse models when TSLP is administered along with an allergen, and TSLP appears to perpetuate a TH2 type of response to the allergen.
The fact that atopic patients have increased susceptibility to Staphylococcal infections is not surprising, as they often have a compromised skin barrier. In atopic skin diseases, TSLP is likely to be detrimental, by serving to promote a TH2 response that increases the allergic response, but in normal skin (or even in atopic skin disease) our data suggest that TSLP might play a protective role by promoting host defense by enhancing neutrophil killing of these pathogens in the skin.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: We think that understanding the role of TSLP at different sites and in different contexts of infection/disease states is important to clarify the roles played by TSLP. TSLP is often thought of as primarily a TH2 promoting cytokine, but our study indicates another role for this cytokine.
Additionally, we think that the link between TSLP and complement is an important area to further study and understand, as both anti-TSLP antibodies and complement inhibitors are currently being evaluated and used in clinical studies.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
EE West, R Spolski, M Kademian, ZX Yu, C Kemper. WJ Leonard. A novel TSLP-complement axis mediates killing of methicillin-resistant Staphylococcus aureus by neutrophils. Science Immunology (DOI: 10.1126/sciimmunol.aaf8471)
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