Immunotherapy to combat skin infections

摘要 手术后发生的手术部位感染是医疗保健的最大单一原因- 相关感染，影响美国的157,500名患者，造成数十亿美元的损失 每年一次。随着感染皮肤的细菌之间迅速出现多重耐药性， 包括不断增长的糖尿病患者人口，而且没有新的抗生素推出 在这条管道上，临床上迫切需要替代策略来抗击皮肤感染。在……里面 鉴于最近免疫疗法在治疗几种致命癌症方面的成功， 宿主自身的免疫系统来对抗皮肤感染是一种可行的可能性。我们推断出一个 皮肤免疫治疗的潜在靶点是肥大细胞(MC)。事实上，我们已经发现 皮肤中的MCs可以通过MCs的招募来促进细菌的清除。最近 我们发现，在真皮中靠近MC的树突状细胞亚群发挥作用 通过诱导受伤皮肤快速再上皮化，在伤口愈合中起关键作用。自创以来 在细菌从受感染的皮肤清除之后，我们假设这些树突状细胞 可能有助于MC激活后的伤口愈合。我们之前已经证明过 肥大细胞激活剂(MCAS)是一种强大且安全的佐剂 疫苗。在这里，我们假设将相同的MCAS应用于受感染的皮肤 即使不使用抗生素，也能加速细菌清除和伤口愈合。至 验证这些想法并扩展我们的研究我们建议如下：(I)调查 巨噬细胞和树突状细胞在促进细菌清除和创面愈合中的多方面作用 以及(2)调查MCAS在促进细菌清除和伤口愈合方面的使用 被几种主要皮肤病原体感染后，建立潜在的基础 为了这种保护。

Abstract Surgical site infections occurring post-operatively are the single largest cause of healthcare- associated infections, affecting 157,500 patients in the US and costing billions of dollars annually. With the rapid emergence of multi-resistance among bacteria infecting the skin, including the growing population of diabetic patients, and with no new antibiotics coming down the pipeline, there is a dire clinical need for alternate strategies to combat skin infections. In view of the recent successes of immunotherapy in curing several lethal cancers, coopting the host's own immune system to combat skin infections is a viable possibility. We reasoned that a potential target of immunotherapy in the skin are mast cells (MCs). Indeed, we have found that MCs in the skin can contribute to bacterial clearance through the recruitment of MCs. Recently we discovered that a subset of dendritic cells found in close proximity to MCs in the dermis play a key role in wound healing by inducing rapid reepithelization of injured skin. Since wound healing follows bacterial clearance from infected skin, we hypothesis that these dendritic cells may contribute to wound healing following MC activation. We have previously demonstrated that mast cell activators (MCAs) are powerful and safe adjuvants when combined with various vaccines. Here, we have hypothesized that applying the same MCAs to infected skin would accelerate bacterial clearance and wound healing even without the use of antibiotics. To validate these ideas and extend our studies we propose the following: (i) investigate the multifaceted role of MCs and dendritic cells in promoting bacterial clearance and wound healing and (ii) Investigate the use of MCAs in promoting clearance of bacteria and wound healing following infection by several prominent skin pathogens and establishing the underlying basis for this protection.