Axl and MerTK receptor tyrosine kinases maintain macrophage efferocytic capacity in the presence of viral triggersCitation formats

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Axl and MerTK receptor tyrosine kinases maintain macrophage efferocytic capacity in the presence of viral triggers. / Grabiec, Aleksander M; Goenka, Anupam; Fife, Mark E; Fujimori, Toshifumi; Hussell, Tracy.

In: European journal of immunology, Vol. 48, No. 5, 05.2018.

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Grabiec, Aleksander M ; Goenka, Anupam ; Fife, Mark E ; Fujimori, Toshifumi ; Hussell, Tracy. / Axl and MerTK receptor tyrosine kinases maintain macrophage efferocytic capacity in the presence of viral triggers. In: European journal of immunology. 2018 ; Vol. 48, No. 5.

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@article{ed60f4d558c1497a9b61f832dfc18ace,
title = "Axl and MerTK receptor tyrosine kinases maintain macrophage efferocytic capacity in the presence of viral triggers",
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 (IFNα) and the TLR3 ligand poly(I:C), specifically induced Axl expression and promoted binding of the bridging molecule Gas6. Axl induction by IFNα and poly(I:C) was associated with higher MDM efferocytic capacity compared to cells treated with other pro-inflammatory stimuli, such as LPS and IFNγ. 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.",
keywords = "Macrophages, Efferocytosis, TAM receptors, Axl , Cellular immunology",
author = "Grabiec, {Aleksander M} and Anupam Goenka and Fife, {Mark E} and Toshifumi Fujimori and Tracy Hussell",
year = "2018",
month = "5",
doi = "10.1002/eji.201747283",
language = "English",
volume = "48",
journal = "European journal of immunology",
issn = "1521-4141",
publisher = "John Wiley & Sons Ltd",
number = "5",

}

RIS

TY - JOUR

T1 - Axl and MerTK receptor tyrosine kinases maintain macrophage efferocytic capacity in the presence of viral triggers

AU - Grabiec, Aleksander M

AU - Goenka, Anupam

AU - Fife, Mark E

AU - Fujimori, Toshifumi

AU - Hussell, Tracy

PY - 2018/5

Y1 - 2018/5

N2 - 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 (IFNα) and the TLR3 ligand poly(I:C), specifically induced Axl expression and promoted binding of the bridging molecule Gas6. Axl induction by IFNα and poly(I:C) was associated with higher MDM efferocytic capacity compared to cells treated with other pro-inflammatory stimuli, such as LPS and IFNγ. 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.

AB - 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 (IFNα) and the TLR3 ligand poly(I:C), specifically induced Axl expression and promoted binding of the bridging molecule Gas6. Axl induction by IFNα and poly(I:C) was associated with higher MDM efferocytic capacity compared to cells treated with other pro-inflammatory stimuli, such as LPS and IFNγ. 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.

KW - Macrophages

KW - Efferocytosis

KW - TAM receptors

KW - Axl

KW - Cellular immunology

U2 - 10.1002/eji.201747283

DO - 10.1002/eji.201747283

M3 - Article

VL - 48

JO - European journal of immunology

JF - European journal of immunology

SN - 1521-4141

IS - 5

ER -