Enveloped viruses disable innate immune responses in dendritic cells by direct activation of TAM receptors
S Bhattacharyya, A Zagórska, ED Lew, B Shrestha… - Cell host & …, 2013 - cell.com
S Bhattacharyya, A Zagórska, ED Lew, B Shrestha, CV Rothlin, J Naughton, MS Diamond…
Cell host & microbe, 2013•cell.comUpon activation by the ligands Gas6 and Protein S, Tyro3/Axl/Mer (TAM) receptor tyrosine
kinases promote phagocytic clearance of apoptotic cells and downregulate immune
responses initiated by Toll-like receptors and type I interferons (IFNs). Many enveloped
viruses display the phospholipid phosphatidylserine on their membranes, through which
they bind Gas6 and Protein S and engage TAM receptors. We find that ligand-coated viruses
activate TAM receptors on dendritic cells (DCs), dampen type I IFN signaling, and thereby …
kinases promote phagocytic clearance of apoptotic cells and downregulate immune
responses initiated by Toll-like receptors and type I interferons (IFNs). Many enveloped
viruses display the phospholipid phosphatidylserine on their membranes, through which
they bind Gas6 and Protein S and engage TAM receptors. We find that ligand-coated viruses
activate TAM receptors on dendritic cells (DCs), dampen type I IFN signaling, and thereby …
Summary
Upon activation by the ligands Gas6 and Protein S, Tyro3/Axl/Mer (TAM) receptor tyrosine kinases promote phagocytic clearance of apoptotic cells and downregulate immune responses initiated by Toll-like receptors and type I interferons (IFNs). Many enveloped viruses display the phospholipid phosphatidylserine on their membranes, through which they bind Gas6 and Protein S and engage TAM receptors. We find that ligand-coated viruses activate TAM receptors on dendritic cells (DCs), dampen type I IFN signaling, and thereby evade host immunity and promote infection. Upon virus challenge, TAM-deficient DCs display type I IFN responses that are elevated in comparison to wild-type cells. As a consequence, TAM-deficient DCs are relatively resistant to infection by flaviviruses and pseudotyped retroviruses, but infection can be restored with neutralizing type I IFN antibodies. Correspondingly, a TAM kinase inhibitor antagonizes the infection of wild-type DCs. Thus, TAM receptors are engaged by viruses in order to attenuate type I IFN signaling and represent potential therapeutic targets.
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