The complement system is an ancient antimicrobial defense system, whereas the cytokine TSLP is associated with influencing lymphocyte development and contributing to type 2 immune responses and is particularly abundant in skin. In Science Immunology, West et al. report that TSLP serves a role in antibacterial responses by boosting neutrophil production of reactive oxygen species. Both mouse neutrophils and human neutrophils express the receptor for TSLP, and its expression increases after exposure to Staphylococcus aureus. Mice deficient in this receptor show defective neutrophil-mediated killing of bacteria and are more sensitive to skin infection. TLSP-augmented neutrophil responses require the complement protein C5. Signaling via the TSLP receptor upregulates expression of the receptor for C5a, and C5 signaling acts in synergy with TLSP to enhance reactive-oxygen-species-mediated killing of S. aureus and Streptococcus pyogenes. Hence, TSLP and complement activation provide enhanced antibacterial responses during skin infection.

Sci. Immunol. 1, eaaf8471 (2016)