Department of Medicine, Division of Infectious Diseases and Immunology; UMass Metabolic Network; Department of Pathology; Horae Gene Therapy Center; Department of Pediatrics, Division of Pediatric Pulmonology; Graduate School of Biomedical Sciences, Immunology and Microbiology Program and MD/PhD Program
Bacterial Infections and Mycoses | Biochemistry | Cell Biology | Cellular and Molecular Physiology | Immunology of Infectious Disease | Immunopathology | Molecular Biology | Pulmonology | Respiratory Tract Diseases
Aspergillus fumigatus causes invasive pulmonary disease in immunocompromised hosts and allergic asthma in atopic individuals. We studied the contribution of lung eosinophils to these fungal diseases. By in vivo intracellular cytokine staining and confocal microscopy, we observed that eosinophils act as local sources of IL-23 and IL-17. Remarkably, mice lacking eosinophils had a >95% reduction in the percentage of lung IL-23p19+ cells as well as markedly reduced IL-23 heterodimer in lung lavage fluid. Eosinophils killed A. fumigatus conidia in vivo. Eosinopenic mice had higher mortality rates, decreased recruitment of inflammatory monocytes, and decreased expansion of lung macrophages after challenge with conidia. All of these functions underscore a potential protective role for eosinophils in acute aspergillosis. Given the postulated role for IL-17 in asthma pathogenesis, we assessed whether eosinophils could act as sources of IL-23 and IL-17 in models where mice were sensitized to either A. fumigatus antigens or ovalbumin (OVA). We found IL-23p19+ IL-17AF+ eosinophils in both allergic models. Moreover, close to 95% of IL-23p19+ cells and >90% of IL-17AF+ cells were identified as eosinophils. These data establish a new paradigm in acute and allergic aspergillosis whereby eosinophils act not only as effector cells but also as immunomodulatory cells driving the IL-23/IL-17 axis and contributing to inflammatory cell recruitment.
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DOI of Published Version
PLoS Pathog. 2017 Jan 17;13(1):e1006175. eCollection 2017 Jan. Link to article on publisher's site
Guerra, Evelyn V. Santos; Lee, Chrono K.; Specht, Charles A.; Yadav, Bhawna; Huang, Haibin; Akalin, Ali; Huh, Jun R.; Mueller, Christian; and Levitz, Stuart M., "Central Role of IL-23 and IL-17 Producing Eosinophils as Immunomodulatory Effector Cells in Acute Pulmonary Aspergillosis and Allergic Asthma" (2017). UMass Metabolic Network Publications. 92.
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