Merocytophagy is an integrin-stabilized macrophage response to microbes reliant on Syk signaling

TL;DR

Macrophages use a process called merocytophagy to transfer bacteria and cytosolic content from other cells, and this process is supported by integrin proteins and Syk signaling.

Contribution

This study identifies Syk signaling and integrin proteins as key components in merocytophagy during microbial infection.

Findings

Merocytophagy is stimulated by bacteria through pattern recognition receptors.

Syk signaling is essential for merocytophagy during Francisella tularensis infection.

Integrin proteins like α4, β1, ICAM-1, and CD44 are upregulated during merocytophagy.

Abstract

Macrophages and dendritic cells acquire bacteria and cytosolic content from other cells without killing the donor cell through a trogocytosis-associated process termed merocytophagy. While characteristics of this behavior have been partially identified, the mechanism and potential contribution to the response to infection are unclear. Here, we reveal that a wide range of distinct species of bacteria stimulate enhanced merocytophagy in macrophages through pattern recognition receptor (PRR). Further, we found that cell-to-cell transfer in response to Francisella tularensis infection occurs in a predominantly MyD88-independent manner, relying on spleen tyrosine kinase (Syk) activity. Syk signaling during this response also results in increased surface expression of cell-to-cell adhesion proteins integrin α4, integrin β1, ICAM-1 and CD44 at the site of merocytophagy transfer, and depleting these surface molecules impairs merocytophagic cell-to-cell transfer. Altogether, our data demonstrate that merocytophagy is a host response to infection facilitated by tight cell-to-cell binding which molecularly resembles an immunological synapse between macrophages.

Image created using elements from NIAID Visual and Medical Arts, Proteins Collection. Courtesy of NIAID BIOART Source (https://bioart.niaid.nih.gov/).

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