title: 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-β, IL-1β, IL-6, and TNF-α in the presence of 1MT. These findings provide important knowledge for the role of IDO during initial host response to influenza infection.
authors.affiliation: Department of Infectious Diseases, University of Georgia, Athens, Georgia, USA.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Fox
authors.affiliation: Department of Infectious Diseases, University of Georgia, Athens, Georgia, USA.
authors.forename: Leo K
authors.initials: LK
authors.lastname: Sage
authors.affiliation: Department of Infectious Diseases, University of Georgia, Athens, Georgia, USA.
authors.forename: Spencer
authors.initials: S
authors.lastname: Poore
authors.affiliation: Department of Infectious Diseases, University of Georgia, Athens, Georgia, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Johnson
authors.affiliation: Department of Infectious Diseases, University of Georgia, Athens, Georgia, USA.
authors.forename: S Mark
authors.initials: SM
authors.lastname: Tompkins
authors.affiliation: Department of Infectious Diseases, University of Georgia, Athens, Georgia, USA ratripp@uga.edu.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Tripp
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007249:Inflammation; D053122:Influenza A Virus, H3N2 Subtype; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D009976:Orthomyxoviridae Infections / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D051192:Receptors, Pattern Recognition / Q000096:biosynthesis* / Q000235:genetics; D013997:Time Factors; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000494:pharmacology; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis / Q000235:genetics
chemical_list: D016207:Cytokines; D004791:Enzyme Inhibitors; C583637:IDO1 protein, mouse; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D009687:Nuclear Proteins; D051192:Receptors, Pattern Recognition; D014364:Tryptophan; D044767:Ubiquitin-Protein Ligases; C418046:Peli1 protein, mouse; C525396:1-methyltryptophan
keywords: 1MT; TLR; alveolar macrophages; cytokines