AXL receptor tyrosine kinase is required for T cell priming and antiviral immunity

Elife. 2016 Jun 28;5:e12414. doi: 10.7554/eLife.12414.

Abstract

The receptor tyrosine kinase (RTK) AXL is induced in response to type I interferons (IFNs) and limits their production through a negative feedback loop. Enhanced production of type I IFNs in Axl(-/-) dendritic cells (DCs) in vitro have led to speculation that inhibition of AXL would promote antiviral responses. Notwithstanding, type I IFNs also exert potent immunosuppressive functions. Here we demonstrate that ablation of AXL enhances the susceptibility to infection by influenza A virus and West Nile virus. The increased type I IFN response in Axl(-/-) mice was associated with diminished DC maturation, reduced production of IL-1β, and defective antiviral T cell immunity. Blockade of type I IFN receptor or administration of IL-1β to Axl(-/-) mice restored the antiviral adaptive response and control of infection. Our results demonstrate that AXL is essential for limiting the immunosuppressive effects of type I IFNs and enabling the induction of protective antiviral adaptive immunity.

Keywords: AXL RTK; IL-1β; West Nile virus; dendritic cell; immunology; influenza A virus; mouse; type I interferons; virus.

Publication types

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

MeSH terms

  • Animals
  • Cells, Cultured
  • Disease Models, Animal
  • Influenza A virus / immunology*
  • Interferon Type I / metabolism
  • Lymphocyte Activation*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Orthomyxoviridae Infections / immunology
  • Proto-Oncogene Proteins / metabolism*
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • T-Lymphocytes / immunology*
  • West Nile Fever / immunology
  • West Nile virus / immunology*

Substances

  • Interferon Type I
  • Proto-Oncogene Proteins
  • Receptor Protein-Tyrosine Kinases
  • axl receptor tyrosine kinase