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

Autor: Edward T Schmid, Iris K Pang, Eugenio A Carrera Silva, Lidia Bosurgi, Jonathan J Miner, Michael S Diamond, Akiko Iwasaki, Carla V Rothlin
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: eLife, Vol 5 (2016)
Druh dokumentu: article
ISSN: 2050-084X
DOI: 10.7554/eLife.12414
Popis: 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.
Databáze: Directory of Open Access Journals