Decreased IDO1-dependent tryptophan metabolism in aged lung during influenza.
Journal
The European respiratory journal
ISSN: 1399-3003
Titre abrégé: Eur Respir J
Pays: England
ID NLM: 8803460
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
26
02
2020
accepted:
08
11
2020
pubmed:
28
11
2020
medline:
6
7
2021
entrez:
27
11
2020
Statut:
epublish
Résumé
Influenza epidemics remain a leading cause of morbidity and mortality worldwide. In the current study, we investigated the impact of chronological ageing 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-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.
Identifiants
pubmed: 33243840
pii: 13993003.00443-2020
doi: 10.1183/13993003.00443-2020
pmc: PMC8147522
mid: NIHMS1691984
pii:
doi:
Substances chimiques
Indoleamine-Pyrrole 2,3,-Dioxygenase
0
Kynurenine
343-65-7
Tryptophan
8DUH1N11BX
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NHLBI NIH HHS
ID : K08 HL138285
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG052530
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG056699
Pays : United States
Informations de copyright
Copyright ©ERS 2021. For reproduction rights and permissions contact permissions@ersnet.org.
Déclaration de conflit d'intérêts
Conflict of interest: S.J. Cho has nothing to disclose. Conflict of interest: K.S. Hong has nothing to disclose. Conflict of interest: E. Schenck has nothing to disclose. Conflict of interest: S. Lee has nothing to disclose. Conflict of interest: R. Harris has nothing to disclose. Conflict of interest: J. Yang has nothing to disclose. Conflict of interest: A.M.K. Choi has nothing to disclose. Conflict of interest: H. Stout-Delgado has nothing to disclose.
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