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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