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- W4313373590 startingPage "70.1" @default.
- W4313373590 abstract "Abstract Influenza remains a leading cause of morbidity and mortality, with highest incidence of hospitalization and death occurring in persons >65 years of age. The goal of this study was to interrogate biochemical profiles manifested in lung tissue originating from young adult and aged adult mice over the course of infection, with the aim of characterizing metabolic migration in lung during influenza. There was heightened inflammation, cellular infiltration, and alveolitis present in the aged lung that corresponded with increased viral titers, morbidity, and mortality. Focusing on the biochemical and pathway changes illustrated an important role for kynurenine and tryptophan metabolism in modulating lung specific immune responses to influenza. There was a significant decrease in kynurenine production in aged alveolar macrophages by day 7 post influenza infection that was associated with increased inflammatory and diminished regulatory responses. Despite a rapid increase in IDO1 expression in young, there was impaired expression and activity in aged macrophages and lung during the course of infection. Age-associated mitochondrial dysfunction contributed to changes in IDO1 expression and decreased kynurenine production in aged lung and alveolar macrophages and resulted in alternate immunometabolic signaling and heightened pro-inflammatory responses. Treatment with a mitochondrial targeted antioxidant improved IDO1 mediated production of kynurenine as well as ameliorated mortality in aged mice. Taken together, our data provide additional evidence as to why older persons are more susceptible to influenza and suggest a possible therapeutic to improve immunometabolic responses in this population." @default.
- W4313373590 created "2023-01-06" @default.
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- W4313373590 date "2020-05-01" @default.
- W4313373590 modified "2023-10-05" @default.
- W4313373590 title "Essential Role of Indoleamine 2, 3-dioxygenase 1 (<i>IDO1</i>) in Metabolic Programming of Innate Immune Responses in Aged Lung during Influenza" @default.
- W4313373590 doi "https://doi.org/10.4049/jimmunol.204.supp.70.1" @default.
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