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- W4313404849 abstract "Abstract Influenza infected patients admitted to the ICU are at significant risk of developing secondary Aspergillus fumigatus (Af) infections, termed influenza-associated pulmonary aspergillosis (IAPA). IAPA affects both immunocompromised and immunocompetent patients, causing a higher morbidity and mortality −50–72% mortality rate–in comparison to other secondary infections. Influenza-induced secondary bacterial infections have been extensively studied, yet little is known about IAPA pathogenesis. We have developed a murine IAV-Af superinfection model in which immunocompetent C57BL/6J mice infected with influenza A virus (IAV) results in increased susceptibility to secondary Af challenge. IAV infection 6 days, but not 3 days, prior to Af challenge causes IAPA in these mice with significant fungal growth and germination leading to increased mortality. With this murine model of IAPA, we examined the potential role of cytokine dysregulation in driving IAV infection to secondary Af challenge. We observed a significant reduction in IAV-induced interferon gamma (IFNγ), which may be associated with impaired immune response during IAV-Af coinfection. However, IAPA infected C57BL/6J and Ifngr−/− mice developed similar disease. IAV-Af superinfected mice produce elevated TNFα during superinfection in comparison to IAV infection. Since myeloid immune cells stimulated with these cytokines have reduced bactericidal activities in COVID-19 patients this combination has the potential to similarly impair IAPA immune responses. Using our novel IAPA model we will assess the role of IFN dysfunction on innate immune cell populations, thereby increasing susceptibility to secondary Af infection by single cell RNA sequencing. Supported by grant from NIH (1 R21 AI152019-1)" @default.
- W4313404849 created "2023-01-06" @default.
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- W4313404849 date "2022-05-01" @default.
- W4313404849 modified "2023-09-25" @default.
- W4313404849 title "Influenza-induced cytokine response predisposes hosts to secondary <i>Aspergillus fumigatus</i> infections" @default.
- W4313404849 doi "https://doi.org/10.4049/jimmunol.208.supp.58.33" @default.
- W4313404849 hasPublicationYear "2022" @default.
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