Inhibition of indoleamine 2,3-dioxygenase enhances the T-cell response to influenza virus infection

Julie M. Fox, Leo K. Sage, Lei Huang, James Barber, Kimberly D. Klonowski, Andrew L. Mellor, S. Mark Tompkins, Ralph A. Tripp

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1451-1461
Number of pages11
JournalJournal of General Virology
Volume94
Issue numberPART7
DOIs
StatePublished - Jul 1 2013

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Indoleamine-Pyrrole 2,3,-Dioxygenase
Virus Diseases
Orthomyxoviridae
T-Lymphocytes
Tryptophan
Human Influenza
Kynurenine
Lung
Influenza A virus
Infection
Inbred C57BL Mouse
Vaccination

ASJC Scopus subject areas

  • Virology

Cite this

Fox, J. M., Sage, L. K., Huang, L., Barber, J., Klonowski, K. D., Mellor, A. L., ... Tripp, R. A. (2013). Inhibition of indoleamine 2,3-dioxygenase enhances the T-cell response to influenza virus infection. Journal of General Virology, 94(PART7), 1451-1461. https://doi.org/10.1099/vir.0.053124-0

Inhibition of indoleamine 2,3-dioxygenase enhances the T-cell response to influenza virus infection. / Fox, Julie M.; Sage, Leo K.; Huang, Lei; Barber, James; Klonowski, Kimberly D.; Mellor, Andrew L.; Tompkins, S. Mark; Tripp, Ralph A.

In: Journal of General Virology, Vol. 94, No. PART7, 01.07.2013, p. 1451-1461.

Research output: Contribution to journalArticle

Fox, JM, Sage, LK, Huang, L, Barber, J, Klonowski, KD, Mellor, AL, Tompkins, SM & Tripp, RA 2013, 'Inhibition of indoleamine 2,3-dioxygenase enhances the T-cell response to influenza virus infection', Journal of General Virology, vol. 94, no. PART7, pp. 1451-1461. https://doi.org/10.1099/vir.0.053124-0
Fox, Julie M. ; Sage, Leo K. ; Huang, Lei ; Barber, James ; Klonowski, Kimberly D. ; Mellor, Andrew L. ; Tompkins, S. Mark ; Tripp, Ralph A. / Inhibition of indoleamine 2,3-dioxygenase enhances the T-cell response to influenza virus infection. In: Journal of General Virology. 2013 ; Vol. 94, No. PART7. pp. 1451-1461.
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