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

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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.