537 Neutrophil-intrinsic TNF receptor signaling directs immunity against staphylococcus aureus

Staphylococcus aureus is the leading cause of skin and soft tissue infections has become a major health burden due to emergence antibiotic-resistant strains. Tumor necrosis factor (TNF) proinflammatory cytokine that rapidly induced upon S. exposure whose inhibition associated with increased risk in humans. However, contribution TNF cognate receptors, TNFR1 TNFR2, host defense against unclear. Therefore, determine role signaling, we used an vivo mouse model infection whereby TNF, TNFR1, or TNFR2 deficient mice wildtype (wt) were intradermally injected bioluminescent monitored for 14 days. exhibited significantly bacterial burdens lesions compared wt mice, suggesting have non-redundant roles TNF-mediated immunity. Furthermore, identified neutrophils (PMNs) as predominant expressing cells. To importance PMN-intrinsic TNFR adoptively transferred PMNs into which reduced lesion sizes mice. We next examined differential on PMN-mediated defense, through discovered was crucial PMN recruitment abscess formation, whereas critical PAD4-dependent neutrophil extracellular trap formation prevention dissemination. Taken together, these findings indicated directed immunity via implications development novel immune-based therapies alternatives antibiotic treatment potentially other infections.