AXL receptor tyrosine kinase is required for T cell priming and antiviral immunity
Edward T Schmid,
Iris K Pang,
Eugenio A Carrera Silva,
Lidia Bosurgi,
Jonathan J Miner,
Michael S Diamond,
Akiko Iwasaki,
Carla V Rothlin
Affiliations
Edward T Schmid
Department of Immunobiology, School of Medicine, Yale University, New Haven, United States
Iris K Pang
Department of Immunobiology, School of Medicine, Yale University, New Haven, United States
Eugenio A Carrera Silva
Department of Immunobiology, School of Medicine, Yale University, New Haven, United States
Lidia Bosurgi
Department of Immunobiology, School of Medicine, Yale University, New Haven, United States
Jonathan J Miner
Department of Medicine, Washington University School of Medicine, St Louis, United States
Michael S Diamond
Department of Molecular Microbiology, Washington University School of Medicine, St Louis, United States; Department of Pathology and Immunology, Washington University School of Medicine, St Louis, United States; The Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St Louis, United States
Department of Immunobiology, School of Medicine, Yale University, New Haven, United States; Howard Hughes Medical Institute, Yale University, New Haven, United States
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.
