Th17 Cytokines and Lung Immunity

Th17 细胞因子和肺部免疫

• 批准号: 9193101
• 负责人: JAY K KOLLS
• 金额: $ 26.39万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9193101
• 关键词: Acetylation; Adoptive Transfer; Antigens; Aspergillus fumigatus; B-Lymphocytes; Bacteria; Bacterial Infections; Bacterial Pneumonia; Bromodomain; Cells; Chromatin; Clinical; Communication; Data; Deposition; Development; Drug resistance; Emigrations; Enterobacteriaceae; Epithelial; Epithelial Cells; Epithelium; Family; Family member; Fostering; Funding; Generations; Genetic Transcription; Histones; Host Defense Mechanism; Human; Immunity; Immunization; Immunology; Infection; Instruction; Interleukin-17; Interleukin-6; Klebsiella pneumonia bacterium; Knockout Mice; Lung; Lysine; MS4A1 gene; Mediating; Membrane Proteins; Modeling; Mucosal Immunity; Mus; Neutrophil Infiltration; Pathway interactions; Pneumonia; Process; Proliferating; Proteins; Pseudomonas aeruginosa; Public Health; Recombinants; Regulation; Research; Resistance; Serotyping; Shapes; Signal Transduction; Source; Specificity; T-Lymphocyte; Testing; Therapeutic; Time; Vaccination; Vaccines; Work; antimicrobial; chromatin modification; cystic fibrosis patients; cytokine; exosome; inhibitor/antagonist; interleukin-22; interleukin-23; killings; macrophage; member; mouse model; mucosal vaccination; neutrophil; novel therapeutics; pathogen; prevent; resistance mechanism; response; vaccin protein; vaccine response; vaccine-induced immunity; γδ T cells

Bacterial pneumonia is an important clinical problem and host defense mechanisms against pneumonia are not fully understood. Data from the prior funding period using a murine model of Klebsiella pneumoniae infection has shown that bacterial deposition in the lung results in the release of the T-cell derived cytokines 1L-17A and 1L-17F, both of which can mediate neutrophil recruitment into the lung. Moreover, IL-22 is produced which can activate STATS in epithelial cells and augment epithelial barrier function as well as the induction of antimicrobial proteins. A critical source of early IL-17 is γδ T-cells but upon vaccination the cellular source of IL-17 shifts to Th17 cells. These cells not only recognize serotype 2 K. pneumoniae but also proliferate in response to other serotypes of K. pneumoniae but also to other phylogenetlcally related bacteria such as members of the enterobacteriaceae family. Thus Th17 cells can provide serotype independent immunity against clades of bacteria. In this renewal we test the hypothesis that vaccine induced Th17 cells can mediate serotype independent immunity against K. pneumoniae (and other related pathogens) by signaling through the lung epithelium. We also examine if these vaccine responses can be elicited by specific subunit antigens such as outer membrane proteins as well as secreted bacterial exososmes. Taken together the research will foster the development of new treatment for bacterial infections that have demonstrated a clear issue of drug resistance. Moreover the proposed work will continue to advance our understanding of mucosal immunity in the lung. RELEVANCE (See instructions): Bacterial pneumonia remains a significant public health concern. The extension of this proposal will study resistance mechanisms in the lung. By understanding normal resistance pathways, we hope that these pathways can be exploited for new therapies to prevent or treat bacterial pneumonia.

细菌性肺炎是一个重要的临床问题，也是宿主防御机制 肺炎尚不完全了解。 肺炎感染表明，肺中的双脚病沉积导致T细胞释放 衍生的细胞因子1L-17A和1L-17F，两者都可以介导嗜中性粒细胞募集到肺中。 此外，生产IL-22，可以激活上皮细胞和辅助振荡屏障屏障的统计数据 功能以及抗菌蛋白的指示。 疫苗接种后，IL-17的细胞来源转移到Th17细胞。 K.肺炎，但也响应K.肺炎的其他血清型，但也对其他 系统生殖器相关的细菌，例如肠杆菌科的成员。 在此续签中提供血清型免疫免疫。 疫苗诱导的Th17细胞可以介导针对肺炎链球菌的血清型独立免疫（和肺炎 其他相关病原体）通过通过肺上皮发出信号。 可以通过特定亚基抗原（例如外部）引起反应 细菌外sose骨共同开发了新的双臂治疗方法。 此外，感染表明了毒品的明确问题。 继续促进我们对肺粘膜免疫的理解。 相关性（请参阅教学）： 细菌性肺炎仍然是一个重要的公共卫生问题。 通过了解正常的抗性途径，我们希望这些机制 可以利用途径来预防或治疗细菌性肺炎。