Faculty of Biology, Medicine and Health, School of Biological Sciences, Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester, UK.
Faculty of Science and Engineering, School of Materials, University of Manchester, Manchester, UK.
Immun Inflamm Dis. 2020 Jun;8(2):198-210. doi: 10.1002/iid3.295. Epub 2020 Mar 28.
Mast cells (MCs) are tissue-resident immune cells implicated in antibacterial responses. These include chemokine secretion, degranulation, and the release of mast cell-extracellular traps, which are primarily dependent on reactive oxygen species (ROS) production. Our study investigated whether human mast cells (hMCs) develop individual response patterns to bacteria located at different tissue sites: Escherichia coli (gut commensal), Listeria monocytogenes (foodborne intracellular pathogen), Staphylococcus aureus (skin commensal and opportunistic pathogen), and Streptococcus pneumoniae (upper respiratory tract commensal and lung pathogen).
After live bacteria exposure, hMCs were analyzed by a combined flow cytometry assay for degranulation, ROS production, DNA externalization, and for β-hexosaminidase, chemokine, and prostaglandin release.
L. monocytogenes induced hMC degranulation, IL-8 and MCP-1 release coupled with DNA externalization in a novel hMC ROS independent manner. In contrast, S. pneumoniae caused ROS production without DNA release and degranulation. E. coli induced low levels of hMC degranulation combined with interleukin 8 and MCP-1 secretion and in the absence of ROS and DNA externalization. Finally, S. aureus induced hMCs prostaglandin D2 release and DNA release selectively. Our findings demonstrate a novel hMC phenomenon of DNA externalization independent of ROS production. We also showed that ROS production, degranulation, DNA externalization, and mediator secretion occur as independent immune reactions in hMCs upon bacterial encounter and that hMCs contribute to bacterial clearance.
Thus, hMCs exhibit a highly individualized pattern of immune response possibly to meet tissue requirements and regulate bacteria coexistence vs defense.
肥大细胞（MCs）是组织驻留的免疫细胞，参与抗菌反应。这些反应包括趋化因子分泌、脱颗粒和释放肥大细胞细胞外陷阱，主要依赖于活性氧物质（ROS）的产生。我们的研究调查了人类肥大细胞（hMCs）是否对位于不同组织部位的细菌产生个体反应模式：大肠杆菌（肠道共生菌）、李斯特菌（食源性病原体）、金黄色葡萄球菌（皮肤共生菌和机会性病原体）和肺炎链球菌（上呼吸道共生菌和肺部病原体）。
在活细菌暴露后，通过联合流式细胞术分析 hMC 的脱颗粒、ROS 产生、DNA 外渗以及β-己糖胺酶、趋化因子和前列腺素的释放。
李斯特菌诱导 hMC 脱颗粒、IL-8 和 MCP-1 释放，同时伴有 DNA 外渗，这是一种新型的 hMC ROS 非依赖性方式。相比之下，肺炎链球菌引起 ROS 产生而无 DNA 释放和脱颗粒。大肠杆菌诱导 hMC 低水平脱颗粒，伴有白细胞介素 8 和 MCP-1 分泌，而无 ROS 和 DNA 外渗。最后，金黄色葡萄球菌选择性诱导 hMC 前列腺素 D2 释放和 DNA 释放。我们的研究结果表明，hMC 存在一种新型的 DNA 外渗现象，不依赖于 ROS 的产生。我们还表明，ROS 产生、脱颗粒、DNA 外渗和介质分泌在 hMC 遇到细菌时作为独立的免疫反应发生，并且 hMC 有助于细菌清除。
因此，hMC 表现出高度个性化的免疫反应模式，可能是为了满足组织的需求，并调节细菌共存与防御之间的平衡。
