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

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

Author information

1
Department of Immunobiology, School of Medicine, Yale University, New Haven, United States.
2
Department of Medicine, Washington University School of Medicine, St Louis, United States.
3
Department of Molecular Microbiology, Washington University School of Medicine, St Louis, United States.
4
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, United States.
5
The Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St Louis, United States.
6
Howard Hughes Medical Institute, Yale University, New Haven, United States.

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

PMID:
27350258
PMCID:
PMC4924996
DOI:
10.7554/eLife.12414
[Indexed for MEDLINE]
Free PMC Article

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