The National Institute of Allergy and Infectious Diseases awarded Trustees of Dartmouth College $100,228 on February 4, 2027, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to investigate the role of alveolar macrophage mitochondria and peroxisomes in antifungal immune responses against Aspergillus fumigatus infections.
The research addresses how mitochondria and peroxisomes regulate interferon type I and III production in alveolar macrophages exposed to the fungal opportunistic pathogen Aspergillus fumigatus, which causes high-morbidity infections in immunocompromised populations including individuals with AIDS, cancer patients, and those receiving immunosuppressants. The investigator will generate alveolar macrophage models with knocked-down organelles and regulated pathways, then employ in vitro and in vivo assays to characterize effects on the interferon response. In vitro work includes phagocytosis and killing assays, cytokine release quantified by ELISAs, and transcriptional profiles measured by QRT-PCR. In vivo studies will employ an adoptive transfer mouse model in which native alveolar macrophages are depleted and mutant macrophages transferred for implantation. The research will determine the significance of mitochondria and peroxisomes in antifungal phagocytosis, killing, and inflammatory response, and examine the role of MAVS, an adaptor protein localized to both organelles, in functional mitochondrial antifungal interferon response.
Work is performed in Hanover, New Hampshire with a period of performance through August 31, 2029. This is a Project Grant, an assistance type supporting biomedical research and research training in infectious diseases and related areas.