943 Loss of both host-derived antimicrobial peptides and bacteriocin-producing commensals enables survival of Staphylococcus aureus on Th2-inflamed skin

Atopic dermatitis (AD) is susceptible to S. aureus colonization which exacerbates this disease. AD has reduced expression of cathelicidin (Camp) and b-defensin (Defb) antimicrobial peptides (AMPs) compared other inflammatory disorders but the these AMPs still higher in than on normal skin. To understand why increased skin would enable we analyzed Il4ra-/- or WT mice with without MC903-induced Th2 inflammation. scRNA-Seq showed that topical application frequency Il17a+ Th17 subsets enhanced Gata3+ when pretreated MC903. In contrast, shifted back toward Th17-predominant response despite MC903 pretreatment. keratinocytes, scRNAseq identified diminished induction multiple AMP genes such as S1008/9, Lnc2 Camp from treated was associated an increase survival. exposed had greatly keratinocytes relative a 3-log (P<.01) decrease survival, thus supporting central role IL-4Ra suppressing innate immune not explaining We next asked if inflammation inhibited survival coagulase-negative Staphylococcus (CoNS) strains producing bacteriocins (CoNS-Bac+) kill aureus. CoNS-Bac+were 2-8 times more vitro human AMPs, LL-37, DEFB3 DEFB2, CoNS-Bac- (P<.001) protective bacteria were killed by low levels could be produced Th2-inflamed Notably, selective killing CoNS-Bac+ rescued Camp-/- These results show combination both partial loss host elimination CoNS-Bac+during can explain expands