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部分自噬是一种依赖于脾酪氨酸激酶(Syk)信号传导的、由整合素稳定的巨噬细胞对微生物的反应。

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

作者信息

Deobald Kelly N, Steele Shaun P, Dominguez Sedelia R, Whiles Shannon, Kawula Thomas

机构信息

Allen School for Global Health, Washington State University, Pullman, WA, United States.

出版信息

Front Immunol. 2025 Apr 17;16:1565250. doi: 10.3389/fimmu.2025.1565250. eCollection 2025.

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 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.

摘要

巨噬细胞和树突状细胞通过一种称为部分吞噬作用的与胞啃作用相关的过程,在不杀死供体细胞的情况下从其他细胞获取细菌和胞质内容物。虽然这种行为的特征已被部分识别,但该机制及其对感染反应的潜在贡献尚不清楚。在这里,我们揭示了多种不同种类的细菌通过模式识别受体(PRR)刺激巨噬细胞中增强的部分吞噬作用。此外,我们发现对感染的细胞间转移主要以不依赖MyD88的方式发生,依赖于脾酪氨酸激酶(Syk)的活性。在此反应过程中,Syk信号传导还导致在部分吞噬作用转移部位细胞间粘附蛋白整合素α4、整合素β1、细胞间粘附分子1(ICAM-1)和CD44的表面表达增加,耗尽这些表面分子会损害部分吞噬作用的细胞间转移。总之,我们的数据表明,部分吞噬作用是一种由紧密的细胞间结合促进的宿主对感染的反应,其分子机制类似于巨噬细胞之间的免疫突触。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e494/12043706/f3bff40f0e68/fimmu-16-1565250-g001.jpg

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