TY - JOUR T1 - Decreased IDO1 Dependent Tryptophan Metabolism in Aged Lung during Influenza JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.00443-2020 SP - 2000443 AU - Soo Jung Cho AU - Kyung Sook Hong AU - Edward Schenck AU - Stefi Lee AU - Rebecca Harris AU - Jianjun Yang AU - Augustine MK Choi AU - Heather Stout-Delgado Y1 - 2020/01/01 UR - http://erj.ersjournals.com/content/early/2020/11/11/13993003.00443-2020.abstract N2 - Influenza epidemics remain a leading cause of morbidity and mortality worldwide. In the current study, we investigated the impact of chronological aging on tryptophan metabolism in response to influenza infection. Examination of metabolites present in plasma collected from critically ill patients, identified tryptophan metabolism as an important metabolic pathway utilised specifically in response to influenza. Using a murine model of influenza infection to further these findings illustrated that there was decreased production of kynurenine in aged lung in an indoleamine-pyrrole 2,3-dioxygenase (IDO1)-dependent manner that was associated with increased inflammatory and diminished regulatory responses. Specifically, within the first 7 days of influenza, there was a decrease in kynurenine pathway mediated metabolism of tryptophan, which resulted in a subsequent increase in ketone body catabolism in aged alveolar macrophages. Treatment of aged mice with mitoquinol, a mitochondrial targeted antioxidant, improved mitochondrial function and restored tryptophan metabolism. 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.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Ms. Borgese has nothing to disclose.Conflict of interest: Dr. Cho has nothing to disclose.Conflict of interest: Dr. Hong has nothing to disclose.Conflict of interest: Dr. Schenck has nothing to disclose.Conflict of interest: Dr. Lee has nothing to disclose.Conflict of interest: Dr. Harris has nothing to disclose.Conflict of interest: Dr. Yang has nothing to disclose.Conflict of interest: A. M.K.C. is a cofounder, stock holder and serves on the Scientific Advisory Board for Proterris, which develops therapeutic uses for carbon monoxide. A.M.K.C. also has a use patent on CO.Conflict of interest: Dr. Stout-Delgado has nothing to disclose. ER -