Table 1_Merocytophagy is an integrin-stabilized macrophage response to microbes reliant on Syk signaling.xlsx

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.

巨噬细胞（Macrophages）与树突状细胞（dendritic cells）可通过一种与胞啃作用（trogocytosis）相关的过程——胞质噬作用（merocytophagy）——从其他细胞获取细菌及胞质内容物，且不会杀伤供体细胞。尽管该行为的部分特征已被阐明，但其具体分子机制以及在感染应答中的潜在贡献仍不明确。本研究发现，多种不同菌种的细菌可通过模式识别受体（pattern recognition receptor, PRR）增强巨噬细胞的胞质噬作用。进一步研究显示，针对土拉弗朗西斯菌（Francisella tularensis）感染所介导的细胞间转移过程，其主要以髓系分化因子88（MyD88）非依赖的方式进行，且依赖于脾酪氨酸激酶（spleen tyrosine kinase, Syk）的活性。该应答过程中的Syk信号通路还可使胞质噬作用转移位点处的细胞间黏附分子——整合素α4（integrin α4）、整合素β1（integrin β1）、细胞间黏附分子1（ICAM-1）及CD44——的表面表达水平上调；敲低这些表面分子的表达会损害胞质噬作用介导的细胞间转移。综上，本研究数据证实，胞质噬作用是宿主针对感染的一种应答方式，其依赖于紧密的细胞间结合，分子层面上与巨噬细胞间的免疫突触（immunological synapse）相似。