title: Inhibition of indoleamine 2,3-dioxygenase enhances the T-cell response to influenza virus infection.
abstract: Influenza infection induces an increase in the level of indoleamine 2,3-dioxygenase (IDO) activity in the lung parenchyma. IDO is the first and rate-limiting step in the kynurenine pathway where tryptophan is reduced to kynurenine and other metabolites. The depletion of tryptophan, and production of associated metabolites, attenuates the immune response to infection. The impact of IDO on the primary immune response to influenza virus infection was determined using the IDO inhibitor 1-methyl-D,L-tryptophan (1MT). C57BL/6 mice treated with 1MT and infected with A/HKx31 influenza virus had increased numbers of activated and functional CD4⁺ T-cells, influenza-specific CD8⁺ T-cells and effector memory cells in the lung. Inhibition of IDO increased the Th1 response in CD4⁺ T-cells as well as enhanced the Th17 response. These studies show that inhibition of IDO engenders a more robust T-cell response to influenza virus, and suggests an approach for enhancing the immune response to influenza vaccination by facilitating increased influenza-specific T-cell response.
authors.affiliation: Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Fox
authors.affiliation: Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA.
authors.forename: Leo K
authors.initials: LK
authors.lastname: Sage
authors.affiliation: Immunotherapy Center and Department of Medicine, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA.
authors.forename: James
authors.initials: J
authors.lastname: Barber
authors.affiliation: Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA.
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Klonowski
authors.affiliation: Immunotherapy Center and Department of Medicine, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Mellor
authors.affiliation: Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA.
authors.forename: S Mark
authors.initials: SM
authors.lastname: Tompkins
authors.affiliation: Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Tripp
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D009980:Influenza A virus / Q000276:immunology* / Q000472:pathogenicity; D007737:Kynurenine / Q000378:metabolism; D008168:Lung / Q000201:enzymology / Q000821:virology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D014364:Tryptophan / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine; D014364:Tryptophan