Immunotherapy to combat skin infections

免疫疗法对抗皮肤感染

• 批准号: 9906450
• 负责人: Soman N Abraham
• 金额: $ 27.89万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-23 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9906450
• 关键词: Adjuvant; Affect; Amines; Antibiotic Therapy; Antibiotics; Antimicrobial Resistance; Bacteria; Bacterial Infections; Blood Circulation; Burn injury; Cells; Cessation of life; Clinical; Coupled; Cytoplasmic Granules; Data; Dendritic Cells; Dermal; Dermis; Development; Diabetes Mellitus; Environment; Exhibits; Explosion; G-Protein-Coupled Receptors; GTP-Binding Protein alpha Subunits, Gs; Immune; Immune system; Immunotherapeutic agent; Immunotherapy; Infection; Infectious Skin Diseases; Lesion; Location; Malignant Neoplasms; Mediating; Mediator of activation protein; Modeling; Mucous Membrane; Multiple Bacterial Drug Resistance; Mus; Neutrophil Infiltration; Operative Surgical Procedures; Patients; Peptide Hydrolases; Peptides; Play; Population; Postoperative Period; Process; Resistance; Resolution; Role; Site; Skin; Skin wound; Specificity; Staphylococcus aureus; Sterility; Superbug; Surface; Surgical wound; Time; Tissues; Topical application; Vaccines; Wild Type Mouse; Work; Wound Healing; adaptive immune response; bacterial resistance; chemokine; combat; cost; cytokine; diabetic patient; healing; healthcare-associated infections; injured; interest; mast cell; mastoparan; neutrophil; pathogen; recruit; success

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.

抽象的 术后发生的手术部位感染是医疗保健的最大原因 相关感染，影响美国157,500名患者，耗资数十亿美元 每年。随着感染皮肤的细菌中多抗性的快速出现， 包括不断增长的糖尿病患者人群，没有新的抗生素降低 管道，对抗击皮肤感染的替代策略存在巨大的临床需求。在 免疫疗法最近在治愈几种致命癌中取得的成功的看法 宿主自己的免疫系统以对抗皮肤感染是一种可行的可能性。我们认为 皮肤免疫疗法的潜在靶标是肥大细胞（MCS）。确实，我们发现 皮肤中的MC可以通过募集MC来导致细菌清除。最近 我们发现，在真皮玩具中与MC近距离发现的树突状细胞子集 通过诱导受伤的皮肤快速重新上述，在伤口愈合中的关键作用。自伤口以来 愈合遵循感染皮肤的细菌清除，我们假设这些树突状细胞 MC激活后可能有助于伤口愈合。我们以前已经证明了 当与各种 疫苗。在这里，我们假设将相同的MCA应用于感染的皮肤会 即使不使用抗生素，也可以加速细菌清除和伤口愈合。到 验证这些想法并扩展我们的研究，我们提出以下建议：（i）调查 MC和树突状细胞在促进细菌清除和伤口愈合中的多方面作用 （ii）研究MCA在促进细菌清除和伤口愈合中的使用 经过几种突出的皮肤病原体感染并建立基础 为此保护。