Axl and MerTK receptor tyrosine kinases maintain human macrophage efferocytic capacity in the presence of viral triggers

Aleksander M Grabiec, Anu Goenka, Mark E Fife, Toshifumi Fujimori, Tracy Hussell

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

The requirement to remove apoptotic cells is equally important in homeostasis and inflammatory disease. In particular, during viral infections large quantities of infected cells undergo apoptosis and need to be efficiently cleared by phagocytes to prevent secondary necrosis. Although specific roles of several apoptotic cell sensors, such as the TAM (Tyro3, Axl, MerTK) receptor family, have been characterized in mouse models, little is known about their regulation and involvement in apoptotic cell uptake (efferocytosis) by human macrophages under inflammatory conditions. We show that whereas pro-inflammatory stimuli consistently downregulated MerTK expression in human monocyte-derived macrophages (MDMs), stimuli indicative of a viral infection, interferon-α (IFN-α) and the TLR3 ligand poly(I:C), specifically induced Axl expression and promoted binding of the bridging molecule Gas6. Axl induction by IFN-α and poly(I:C) was associated with higher MDM efferocytic capacity compared to cells treated with other pro-inflammatory stimuli, such as LPS and IFN-γ. While MerTK blocking antibody uniformly suppressed apoptotic cell uptake by MDMs, Axl blocking antibody significantly reduced efferocytosis by poly(I:C)-stimulated MDMs, but not by resting MDMs. Our observations demonstrate that Axl induction during viral infections contributes to maintaining macrophage capacity to engulf apoptotic cells, which may have important consequences for resolution of anti-viral immune responses.

Original languageEnglish
Pages (from-to)855-860
Number of pages6
JournalEuropean Journal of Immunology
Volume48
Issue number5
DOIs
Publication statusPublished - May 2018

Bibliographical note

© 2018 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Keywords

  • Apoptosis/immunology
  • Cell Line, Tumor
  • Humans
  • Intercellular Signaling Peptides and Proteins/metabolism
  • Interferon-alpha/immunology
  • Jurkat Cells
  • Macrophages/immunology
  • Phagocytosis/immunology
  • Poly I-C/immunology
  • Proto-Oncogene Proteins/metabolism
  • Receptor Protein-Tyrosine Kinases/metabolism
  • c-Mer Tyrosine Kinase/metabolism

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