Host Responses Toward Influenza Associated Pulmonary Aspergillosis
AuthorsLee, Chrono K.
Faculty AdvisorStuart M. Levitz; Jennifer P. Wang
Academic ProgramImmunology and Microbiology
UMass Chan AffiliationsMedicine
Document TypeDoctoral Dissertation
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AbstractAspergillus fumigatus is a saprophytic fungus that is responsible for causing a wide range of diseases primarily affecting immunocompromised hosts. However, cases of influenza associated pulmonary aspergillosis have been reported and the cause for the lethality remains ambiguous. The aim of this dissertation is to examine the underlining immunology and pathology of influenza associated pulmonary aspergillosis. Utilizing a model of post-influenza aspergillosis, we observed 100% mortality when mice were superinfected with A. fumigatus conidia during early stages of influenza, whereas all mice survived when challenged at later stages. In addition, mice dually infected with influenza and A. fumigatus had elevated levels of proinflammatory cytokines and chemokines compared with control mice. Different than our expectations, histopathology examination did not reveal escalation of inflammation nor increased germination of conidia in the lungs of superinfected mice. Although neutrophil recruitment was dampened when influenza-infected mice were challenged with A. fumigatus, the fungal clearance ability of neutrophils remained intact as reactive oxygen species production was not affected by influenza. Furthermore, the loss of interferon α downstream signals, but not interferon ɣ, increased the lethality of secondary aspergillosis in influenza-infected mice. Taken together, our data suggest that the high mortality rate seen in mice during the early stages of influenza associated pulmonary aspergillosis is multifactorial with dysregulated inflammation being a greater contributor than uncontrollable microbial growth. This discovery opens a new paradigm for investigation and treatments that can be formulated for influenza associated pulmonary aspergillosis.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/52693
RightsCopyright © 2023 Chrono K. Lee
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