Central Role of IL-23 and IL-17 Producing Eosinophils as Immunomodulatory Effector Cells in Acute Pulmonary Aspergillosis and Allergic Asthma

PLoS Pathogens

Charles A. Specht¹  Evelyn Santos Guerra¹  Bhawna Yadav¹  Haibin Huang¹  Chrono K. Lee¹  Jun R. Huh¹  Stuart M. Levitz¹  Ali Akalin²  Christian Mueller³ 

[1] Department of Medicine, University of Massachusetts Medical School, Worcester, MA, United States of America;Department of Pathology, University of Massachusetts Medical School, Worcester, MA, United States of America;Horae Gene Therapy Center and Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA, United States of America

关键词: Eosinophils;    Aspergillus fumigatus;    Mouse models;    Asthma;    Aspergillosis;    Inflammation;    Cytokines;    Cell staining;   

DOI  :  10.1371/journal.ppat.1006175

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY