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

基本信息

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
项目类别：
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

项目摘要

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：项目摘要/摘要呼吸道疾病是全球发病率和死亡率的主要原因之一。尽管有疫苗可用，疾病预防控制中心将百日咳视为一种杀死数百种的复发性传染病在发达国家和发达国家中，每年都有成千上万的婴儿和儿童。很遗憾，无法控制百日咳的咳嗽不是一个孤立的现象，因为也可以看到类似的保护其他呼吸道病原体，例如肺炎球菌。大多数针对呼吸道疫苗策略共同细菌疾病的重点是抗体反应的产生，该反应忽略了T细胞和产生持久保护反应时的粘膜免疫。嗜酸性粒细胞是一种已知的免疫细胞在保护寄生虫（蠕虫）中扮演关键角色（蠕虫），表明功能对病原体的总体免疫反应。最近的研究表明，嗜酸性粒细胞在适应性中起重要作用通过协调胃粘膜中T和B细胞反应的细胞免疫反应，并在维持中粘膜稳态。该项目将利用小鼠的Bordetella支气管肽感染，这是一种可拖动的咳嗽的小动物模型，研究嗜酸性粒细胞作为T细胞反应的驱动力的作用在呼吸道细菌感染中。我们的初步数据表明，清除需要嗜酸性粒细胞小鼠呼吸道支气管the菌的bordetella支气管。此外，缺乏嗜酸性粒细胞的小鼠持续感染，无法分泌促炎性细胞因子，并且无法产生有效的抗体反应，表明嗜酸性粒细胞促进适应性免疫。拟议研究的完成将提高我们对嗜酸性粒细胞生物学的理解以及嗜酸性粒细胞用于驱动T细胞反应的机制。我们预计从我们的工作中获得的知识将确定改进的新目标反对百日咳的疫苗以及可能由呼吸道病原体引起的其他疾病。