Edward T Schmid, Iris K Pang, Eugenio A Carrera Silva, Lidia Bosurgi, Jonathan J Miner, Michael S Diamond, Akiko Iwasaki, Carla V Rothlin
eLife 2016 Jun 28The 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.
Edward T Schmid, Iris K Pang, Eugenio A Carrera Silva, Lidia Bosurgi, Jonathan J Miner, Michael S Diamond, Akiko Iwasaki, Carla V Rothlin. AXL receptor tyrosine kinase is required for T cell priming and antiviral immunity. eLife. 2016 Jun 28;5
PMID: 27350258
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