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Drug analog inhibition of indoleamine 2,3-dioxygenase (IDO) activity modifies pattern recognition receptor expression and proinflammatory cytokine responses early during influenza virus infection.

ABSTRACT: Influenza virus is recognized by PRRs, which are critical in the early response to virus infection and induction of proinflammatory cytokines. IDO is increased in the lung of mice immediately following influenza infection, and the presence of IDO has been shown to mediate immune suppression through depletion of trp and reduction in IL-6 production. To determine the role of IDO activity in the early immune response to influenza infection, IDO activity was inhibited using the synthetic analog, 1MT. The results show that IDO inhibition enhanced proinflammatory cytokine gene and protein expression at 24 and 48 h postinfection, respectively, compared with control-treated mice and affected PRR expression. The enhanced proinflammatory response in the presence of 1MT was attributed to macrophages in the airways, as Raw264.7 and primary AMs showed enhanced production of IFN-?, IL-1?, IL-6, and TNF-? in the presence of 1MT. These findings provide important knowledge for the role of IDO during initial host response to influenza infection.

SUBMITTER: Fox JM

PROVIDER: S-EPMC4138204 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Drug analog inhibition of indoleamine 2,3-dioxygenase (IDO) activity modifies pattern recognition receptor expression and proinflammatory cytokine responses early during influenza virus infection.

Fox Julie M JM Sage Leo K LK Poore Spencer S Johnson Scott S Tompkins S Mark SM Tripp Ralph A RA

Journal of leukocyte biology 20140505 3

Influenza virus is recognized by PRRs, which are critical in the early response to virus infection and induction of proinflammatory cytokines. IDO is increased in the lung of mice immediately following influenza infection, and the presence of IDO has been shown to mediate immune suppression through depletion of trp and reduction in IL-6 production. To determine the role of IDO activity in the early immune response to influenza infection, IDO activity was inhibited using the synthetic analog, 1MT ...[more]

PMID: 24799604

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Project description:Indoleamine 2,3-deoxygenase (IDO) plays an important role in the catabolism of the amino acid tryptophan. Tryptophan and its metabolites are key immune modulators. Increased IDO activity has been observed in various diseases and is associated with worse clinical outcomes. However, comprehensive research regarding its role in cardiac surgery remains limited. Therefore, we aimed to investigate perioperative changes in IDO activity and pathway metabolites, along with their impact on clinical outcomes in adult patients undergoing cardiac surgery. As an observational cohort study conducted at the Inselspital in Bern from January to December 2019, we retrospectively analyzed the data of prospectively collected biobank samples of patients undergoing cardiac surgery with the use of cardiopulmonary bypass. IDO pathway metabolite analysis was conducted by mass spectrometry. Perioperative dynamics were descriptively assessed and associated with pre-defined clinical outcome measures (30-day mortality, 1-year mortality, incidence of stroke and myocardial infarction, and length of hospital stay) through a multi-step exploratory regression analysis. A cohort of 192 adult patients undergoing cardiac surgery with the use of cardiopulmonary bypass were included (median age 67.0, IQR 60.0-73.0, 75.5% male). A significant perioperative decrease in the kynurenine/tryptophan (Kyn/Trp) ratio (-2.298, 95% CI -4.028 to -596, p = 0.009) and significant perioperative dynamics in the associated metabolites was observed. No association of perioperative changes in IDO activity and pathway metabolites with clinical outcomes was found. A significant decrease in the Kyn/Trp ratio among adult patients undergoing cardiac surgery indicates a perioperative downregulation of IDO, which stands in contrast to other pro-inflammatory conditions. Further studies are needed to investigate IDO in the setting of perioperative immunomodulation, which is a key driver of postoperative complications in cardiac surgery patients.

Dataset Information

Drug analog inhibition of indoleamine 2,3-dioxygenase (IDO) activity modifies pattern recognition receptor expression and proinflammatory cytokine responses early during influenza virus infection.

Publications

Drug analog inhibition of indoleamine 2,3-dioxygenase (IDO) activity modifies pattern recognition receptor expression and proinflammatory cytokine responses early during influenza virus infection.

Similar Datasets

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