Immunology and Microbiology, MD/PhD
First Thesis Advisor
Stuart M. Levitz, MD
Aspergillus fumigatus, Asthma, Eosinophils, Interleukin-17, Interleukin-23, Pulmonary Aspergillosis
Dissertations, UMMS; Aspergillus fumigatus; Asthma; Eosinophils; Interleukin-17; Interleukin-23; Pulmonary Aspergillosis
Aspergillus fumigatus is an opportunistic fungal pathogen that causes lethal invasive pulmonary disease in immunocompromised hosts and allergic asthma in sensitized individuals. This dissertation explores how eosinophils may protect hosts from acute infection while driving asthma pathogenesis by co-producing IL-23 and IL-17 in both contexts. In an acute model of pulmonary aspergillosis, eosinophils were observed to associate with and kill A. fumigatus spores in vivo. In addition, eosinopenia was correlated with higher mortality rates, decreased recruitment of inflammatory monocytes to the lungs, and decreased expansion of lung macrophages. As IL-17 signaling must occur on a local level to elicit its stereotypical response, such as the up-regulation of antimicrobial peptides and specific chemokines from stromal cells, eosinophils were discovered to be a significant source of pulmonary IL-17 as well as one of its upstream inducers, IL-23. In the context of asthma, this discovery opens a new paradigm whereby eosinophils might be driving asthma pathogenesis.
Guerra, EV. Eosinophils as Drivers of the IL-23/IL-17 Axis: Implications for Acute Aspergillosis and Allergic Asthma: A Dissertation. (2016). University of Massachusetts Medical School. GSBS Dissertations and Theses. Paper 831. DOI: 10.13028/M2XS3K. http://escholarship.umassmed.edu/gsbs_diss/831
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