Protective role of Indoleamine 2,3 dioxygenase in Respiratory Syncytial Virus associated immune response in airway epithelial cells

Virology. 2017 Dec:512:144-150. doi: 10.1016/j.virol.2017.09.007. Epub 2017 Sep 28.

Abstract

RSV is a major cause of severe lower respiratory infection in infants and young children. With no vaccine yet available, it is important to clarify mechanisms of disease pathogenesis. Since indoleamine-2,3-dioxygenase (IDO) is an immunomodulatory enzyme and is upregulated with RSV infection, we studied it in vivo during infection of BALB/c mice and in vitro in A549 cells. RSV infection upregulated IDO transcripts in vivo and in vitro. IDO siRNA decreased IDO transcripts ~2 fold compared to control siRNA after RSV infection but this decrease did not affect RSV replication. In the presence of IFN-γ, siRNA-induced a decrease in IDO expression that was associated with an increase in virus replication and increased levels of IL-6, IL-8, CXCL10 and CCL4. Thus, our results show IDO is upregulated with RSV infection and this upregulation likely participates with IFN-γ in inhibition of virus replication and suppression of some host cell responses to infection.

Keywords: Chemokine; Cytokine; IDO; Respiratory Syncytial Virus; Tryptophan.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Cytokines / metabolism
  • Female
  • Gene Expression Regulation / physiology
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / genetics
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • RNA Interference
  • Respiratory Syncytial Viruses / immunology*
  • Up-Regulation
  • Virus Replication / physiology

Substances

  • Cytokines
  • Indoleamine-Pyrrole 2,3,-Dioxygenase