Role of eosinophils during bacterial infection

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Project Summary Influx of eosinophils is typically associated with type II responses during allergy. More recent reports indicate that eosinophils have essential immunoregulatory roles, as well as key anti-microbial effects against helminths, viruses, and some bacterial species. However, the mechanisms underlying how eosinophils contribute to eliminating bacteria are understudied, and results are diametrically different depending upon the infecting pathogen and in acute versus chronic infection. In this application, we propose to investigate the role of eosinophils during persistent Salmonella infection within mesenteric lymph nodes (MLNs) of 129X1/Sv/J mice. Our unpublished data show that eosinophils, which we have localized to STm-containing granulomas, increased significantly over the first 8 weeks of Salmonella enterica Typhimurium (STm) infection, correlated with an increase in the eosinophil chemoattractant CCL11. In addition, depletion of eosinophils in STm-infected mice rendered mice more susceptible to infection. Importantly, eosinophil-depleted mice had a significant reduction of IFNγ-producing cells and lower tissue levels of IFNγ compared to IgG2 controls, suggesting that eosinophils contribute to pathogen control by influencing the granuloma microenvironment to be Th1 skewed. Our central hypothesis is that the functions of eosinophils within infected tissues are regulated by microenvironments, such as the granuloma, and function to contain the pathogen during persistent infection. The impact of eosinophils on granuloma formation and pathogen control via the production of extracellular DNA traps and possible manipulation by bacterial virulence factors will be investigated (Aim 1). In addition, we will characterize the immunoregulatory effector functions of eosinophils during STm persistence in the MLNs (Aim 2).