title: Interferon Lambda Upregulates IDO1 Expression in Respiratory Epithelial Cells After Influenza Virus Infection.
abstract: Influenza infection causes an increase in indoleamine 2, 3-dioxygenase (IDO) activity in the lung parenchyma. IDO catabolizes tryptophan into kynurenine, leading to immune dampening. Multiple cell types express IDO, and while IFN-γ upregulates IDO in dendritic cells and macrophages, it is unclear how IDO is affected in respiratory epithelial cells during influenza infection. In this study, the role of IFN-λ in IDO regulation was investigated after influenza infection of respiratory epithelial cells. IDO1 expression increased concurrently with IFN-λ expression. In differentiated NHBE cells, the IDO metabolite was released basolaterally. Recombinant IFN-λ upregulated IDO1 activity, and silencing of IFN-λ decreased IDO1 expression during influenza infection. During IFN-λ stimulation, most differentiated cell types are able to express IDO but during influenza infection, IDO is primarily expressed in uninfected cells. These studies show a role for IDO in the host response to influenza infection, and they provide insights into novel approaches for enhancing vaccine responses and therapeutic approaches.
authors.affiliation: Department of Infectious Diseases, University of Georgia , Athens, Georgia .
authors.forename: Julie M
authors.initials: JM
authors.lastname: Fox
authors.affiliation: Department of Infectious Diseases, University of Georgia , Athens, Georgia .
authors.forename: Jackelyn M
authors.initials: JM
authors.lastname: Crabtree
authors.affiliation: Department of Infectious Diseases, University of Georgia , Athens, Georgia .
authors.forename: Leo K
authors.initials: LK
authors.lastname: Sage
authors.affiliation: Department of Infectious Diseases, University of Georgia , Athens, Georgia .
authors.forename: S Mark
authors.initials: SM
authors.lastname: Tompkins
authors.affiliation: Department of Infectious Diseases, University of Georgia , Athens, Georgia .
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Tripp
mesh_terms: D000818:Animals; D016923:Cell Death; D002460:Cell Line; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism*; D004285:Dogs; D004847:Epithelial Cells / Q000201:enzymology / Q000821:virology*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007251:Influenza, Human / Q000378:metabolism / Q000821:virology; D007372:Interferons; D007378:Interleukins / Q000378:metabolism*; D008168:Lung / Q000473:pathology; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000378:metabolism* / Q000821:virology; D015854:Up-Regulation; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007372:Interferons; D007378:Interleukins; C576710:IDO1 protein, human; C583637:IDO1 protein, mouse; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C511668:interferon-lambda protein, mouse