Department of Dermatology, Johns Hopkins University School of Medicine, 1550 Orleans Street, Baltimore, MD 21287, USA.
Division of Molecular Internal Medicine, Department of Internal Medicine II, University Hospital Würzburg, Würzburg 97080, Germany.
Sci Adv. 2023 Jun 16;9(24):eadf8748. doi: 10.1126/sciadv.adf8748.
is the leading cause of skin and soft tissue infections and is a major health burden due to the emergence of antibiotic-resistant strains. To address the unmet need of alternative treatments to antibiotics, a better understanding of the protective immune mechanisms against skin infection is warranted. Here, we report that tumor necrosis factor (TNF) promoted protection against in the skin, which was mediated by bone marrow-derived immune cells. Furthermore, neutrophil-intrinsic TNF receptor (TNFR) signaling directed immunity against skin infections. Mechanistically, TNFR1 promoted neutrophil recruitment to the skin, whereas TNFR2 prevented systemic bacterial dissemination and directed neutrophil antimicrobial functions. Treatment with a TNFR2 agonist showed therapeutic efficacy against and skin infections, which involved increased neutrophil extracellular trap formation. Our findings revealed nonredundant roles for TNFR1 and TNFR2 in neutrophils for immunity against and can be therapeutically targeted for protection against bacterial skin infections.
是皮肤和软组织感染的主要原因，由于抗生素耐药菌株的出现，给健康带来了重大负担。为了满足替代抗生素治疗的需求，有必要更好地了解针对皮肤感染的保护性免疫机制。在这里，我们报告称，肿瘤坏死因子（TNF）通过骨髓来源的免疫细胞促进了对 的保护。此外，中性粒细胞固有 TNF 受体（TNFR）信号指导针对 皮肤感染的免疫。从机制上讲，TNFR1 促进中性粒细胞向皮肤募集，而 TNFR2 则防止全身性细菌播散并指导中性粒细胞的抗菌功能。用 TNFR2 激动剂治疗可有效治疗 和 皮肤感染，这涉及增加中性粒细胞细胞外陷阱的形成。我们的研究结果揭示了 TNFR1 和 TNFR2 在中性粒细胞中针对 和 免疫的非冗余作用，可作为治疗靶点以防止细菌皮肤感染。
