Eosinophils facilitate bacterial clearance by mediating antibacterial T cell responses in the respiratory tract

嗜酸性粒细胞通过介导呼吸道中的抗菌 T 细胞反应来促进细菌清除

• 批准号: 10360464
• 负责人: Monica Cartelle Gestal
• 金额: $ 25.35万
• 依托单位: LOUISIANA STATE UNIV HSC SHREVEPORT
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10360464
• 关键词: Acellular Vaccines; Animal Model; Anti-Bacterial Agents; Antibodies; Antibody Formation; Antibody Response; Antigen Presentation; Antigen-Presenting Cells; Antigens; Attention; Automobile Driving; B-Lymphocytes; Bacterial Antigens; Bacterial Infections; Biology; Bordetella; Bordetella Infections; Bordetella bronchiseptica; Cells; Centers for Disease Control and Prevention (U.S.); Child; Communicable Diseases; Country; Data; Development; Disease; Excision; Exhibits; FDA approved; Failure; Flow Cytometry; Gastric mucosa; Generations; Goals; Helminths; Homeostasis; Immune; Immune response; Immunity; Immunology; In Vitro; Incidence; Infection; Inflammatory; Interleukin-17; Knowledge; Lead; Lower respiratory tract structure; Lung; Maintenance; Mediating; Modeling; Monitor; Morbidity - disease rate; Mucosal Immunity; Mucous Membrane; Mus; Parasitic infection; Pathologic Processes; Pathway interactions; Pertussis; Play; Production; Respiratory Disease; Respiratory System; Respiratory Tract Infections; Role; Signal Pathway; Signal Transduction; Stomach; Streptococcus pneumoniae; T cell differentiation; T cell response; T-Cell Activation; T-Lymphocyte; Testing; Vaccines; Whole Cell Vaccine; Work; adaptive immune response; adaptive immunity; airway immune response; chronic infection; cytokine; eosinophil; expectation; experimental study; helminth infection; improved; in vivo; insight; mortality; mouse model; novel; pathogen; recruit; respiratory; respiratory pathogen; response; side effect; therapy development; transcriptome; transcriptome sequencing; vaccine access; vaccine strategy

PROJECT 3: PROJECT SUMMARY/ABSTRACT Respiratory diseases are among the major causes of morbidity and mortality worldwide. Despite that vaccines are available, the CDC recognizes Whooping cough as a reemerging infectious disease that kills hundreds of thousands of babies and children each year, both in developed and underdeveloped countries. Unfortunately, the failure to control Whooping cough is not an isolated phenomenon, as a similar lack of protection is seen with other respiratory pathogens, such as pneumococcus. Common to most vaccines strategies against respiratory bacterial diseases is a focus on the generation of antibody responses, which overlooks roles for T cells and mucosal immunity in producing durable protective responses. Eosinophils are a type of immune cell that is known to play pivotal roles in protection against infection by parasitic helminths (worms), indicating a function in the overall immune response to pathogens. Recent studies reveal that eosinophils play important roles in adaptive cellular immune responses by coordinating T and B cell responses in the gastric mucosa, and in maintenance of mucosal homeostasis. This project will make use of Bordetella bronchiseptica infection of mice, a tractable small animal model for Whooping cough, to investigate the role of eosinophils as drivers of the T cell responses in respiratory bacterial infections. Our preliminary data indicate that eosinophils are required for clearance of Bordetella bronchiseptica from the mouse respiratory tract. Moreover, mice lacking eosinophils present with a persistent infection, fail to secrete pro-inflammatory cytokines, and are unable to generate effective antibody responses, suggesting that eosinophils promote adaptive immunity. Completion of the proposed studies will improve our understanding of eosinophil biology and the mechanisms eosinophils use to drive T cell responses. We anticipate that the knowledge gained from our work will identify novel targets for the development of improved vaccines against Whooping cough and possibly other diseases caused by respiratory pathogens.

项目3：项目总结/摘要 呼吸道疾病是全世界发病率和死亡率的主要原因之一。尽管疫苗 疾病预防控制中心承认百日咳是一种重新出现的传染病， 在发达国家和不发达国家，每年都有成千上万的婴儿和儿童死亡。不幸的是， 未能控制百日咳不是一个孤立的现象，因为类似的缺乏保护， 其他呼吸道病原体，如肺炎球菌。大多数针对呼吸道疾病的疫苗策略的共同点 细菌性疾病的重点是抗体反应的产生，忽视了T细胞的作用， 粘膜免疫产生持久的保护性反应。嗜酸性粒细胞是一种免疫细胞， 在保护免受寄生蠕虫（蠕虫）感染方面发挥关键作用，表明在 对病原体的整体免疫反应。最近的研究表明，嗜酸性粒细胞在适应性免疫中起重要作用， 通过协调胃粘膜中的T和B细胞应答，以及维持 粘膜内环境的稳定。本课题将利用支气管败血波氏杆菌感染小鼠， 百日咳的小动物模型，以研究嗜酸性粒细胞作为T细胞应答驱动者的作用 呼吸道细菌感染我们的初步数据表明，嗜酸性粒细胞需要清除 来自小鼠呼吸道的支气管败血波氏杆菌。此外，缺乏嗜酸性粒细胞的小鼠存在一种 持续感染，不能分泌促炎细胞因子，不能产生有效抗体 反应，表明嗜酸性粒细胞促进适应性免疫。完成拟议的研究将 提高我们对嗜酸性粒细胞生物学和嗜酸性粒细胞驱动T细胞反应的机制的理解。 我们预计，从我们的工作中获得的知识将确定新的目标，为发展改善 预防百日咳和其他可能由呼吸道病原体引起的疾病的疫苗。