Polarization of avian macrophages upon avian flavivirus infection

Vet Microbiol. 2021 May:256:109044. doi: 10.1016/j.vetmic.2021.109044. Epub 2021 Mar 23.

Abstract

Avian Tembusu virus (TMUV) is a newly emerging avian pathogenic flavivirus that spreads rapidly, has an expanding host range and undergoes cross-species transmission. Our previous study identified avian monocytes/macrophages as the key targets of TMUV infection, since the infection of host monocytes/macrophages was crucial for the replication, transmission, and pathogenesis of TMUV. The polarization of host macrophages determines the functional phenotypes of macrophages; however, the effect of TMUV infection on macrophage polarization remains unclear. Here, we analysed the expression spectra of the marker genes of macrophage polarization upon TMUV infection in the HD11 chicken macrophage cell line and primary monocytes/macrophages isolated from the peripheral blood of specific pathogen-free (SPF) chickens and ducks. We found that viral replication mainly induced M1 marker genes and triggered nitric oxide (NO) release at different levels, suggesting that TMUV infection led mainly to host macrophages polarizing into the classically activated (M1) type. The NO that was increased upon infection did not function as an antiviral agent against TMUV, since the replication of TMUV in HD11 cells was not affected by the addition of an organic NO donor. Furthermore, upon TMUV infection, polarized HD11 cells exhibited increased migration but reduced phagocytosis, as evidenced by scratch assay and neutral red uptake assay, respectively. Our present study characterized the polarization of host monocytes/macrophages upon TMUV infection, which may lay a foundation for further research on the immune escape mechanism and pathogenic mechanism of TMUV.

Keywords: Avian Tembusu virus; Macrophage polarization; Migration; Nitric oxide; Phagocytosis.

MeSH terms

  • Animals
  • Antiviral Agents
  • Cell Line
  • Cell Movement
  • Cell Polarity
  • Chickens / physiology*
  • Chickens / virology
  • Ducks / physiology*
  • Ducks / virology
  • Flavivirus / immunology*
  • Flavivirus Infections / veterinary*
  • Flavivirus Infections / virology
  • Host Specificity
  • Macrophages / physiology
  • Macrophages / virology
  • Monocytes / physiology
  • Monocytes / virology
  • Nitric Oxide / metabolism
  • Phagocytosis
  • Poultry Diseases / virology*
  • Specific Pathogen-Free Organisms
  • Virus Replication

Substances

  • Antiviral Agents
  • Nitric Oxide

Supplementary concepts

  • Tembusu virus