Human microglia polarization following infection with the Lyme disease spirochete.

IF 2.5 4区 医学 Q1 MEDICINE, GENERAL & INTERNAL
Journal of Investigative Medicine Pub Date : 2025-01-01 Epub Date: 2024-10-18 DOI:10.1177/10815589241290206
Idris Akinlusi, Brian Kan, Ted Shi, Jose Barragan, Carlos Bouchot, Jorge Cervantes
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引用次数: 0

Abstract

Infection with Borrelia burgdorferi can spread and cause central nervous system involvement, known as neuroborreliosis. Microglia phagocytose bacteria, mediate inflammation, and elicit an immune response toward the spirochete. Like other tissue macrophages, microglia can polarize into two different modulatory phenotypes, M1 and M2. We explored human microglial polarization changes upon infection with B. burgdorferi. HMC3 human microglia cell line was infected with B. burgdorferi for 24 h. Expression of polarization markers was evaluated via flow cytometry at 4 and 24 h. Secreted immunological mediators were evaluated using a multiplex ELISA system at 4, 18, and 24 h. An early decrease followed by a later increase in expression of M1 polarization marker iNOS was observed at 4 h, and 24 h, respectively. A decrease in M2 marker CX3CR1 occurred at 24 h. There were no changes in expression of M1 markers CD14, or in M2 markers CD163 and CD206. Multiplex ELISA evidenced an increase in secretion of activation markers MIP-1α, MIP- 1β, IP-10, chemotactic factor MCP-1, M1 polarization cytokine IL-8, and VEGF, at 4, 18, and 24 h. A decrease of iNOS at 4 h of infection suggests a diminished production of reactive nitrogen species that are a critical component of innate defense against infection. Increased iNOS and simultaneously decreased expression of CX3CR1 at 24 h, may suggest initiation of neuroprotective regulation of microglia recruitment to neuroinflammation. The dynamics of major inflammatory cytokines appear to be important in the microglial response to B. burgdorferi and should be further studied as these could become therapeutic targets in neuroborreliosis.

表达:感染莱姆病螺旋体后人类小胶质细胞极化。
博氏包柔氏菌(Borrelia burgdorferi,Bb)感染可传播并导致中枢神经系统受累,即神经包柔病。小胶质细胞吞噬细菌,介导炎症,并引起对螺旋体的免疫反应。与其他组织巨噬细胞一样,小胶质细胞可极化为两种不同的调节表型,即 M1 和 M2。我们探讨了人类小胶质细胞极化在感染 Bb 后的变化。在 4 小时和 24 小时时,通过流式细胞术评估极化标记物的表达。在 4 小时和 24 小时时,分别观察到 M1 极化标志物 iNOS 的表达先减后增。24 小时后,M2 标志物 CX3CR1 表达减少。M1 标志物 CD14 或 M2 标志物 CD163 和 CD206 的表达没有变化。多重酶联免疫吸附试验(Multiplex ELISA)显示,4、18 和 24 小时时,活化标志物 MIP-1α、MIP-1β、IP-10、趋化因子 MCP-1、M1 极化细胞因子 IL-8 和血管内皮生长因子的分泌量增加。24 小时后 iNOS 增加,同时 CX3CR1 表达减少,这可能表明神经保护性调节小胶质细胞招募神经炎症的开始。主要炎症细胞因子的动态似乎在小胶质细胞对 Bb 的反应中很重要,应进一步研究,因为这些细胞因子可能成为神经源性疾病的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Investigative Medicine
Journal of Investigative Medicine 医学-医学:内科
CiteScore
4.90
自引率
0.00%
发文量
111
审稿时长
24 months
期刊介绍: Journal of Investigative Medicine (JIM) is the official publication of the American Federation for Medical Research. The journal is peer-reviewed and publishes high-quality original articles and reviews in the areas of basic, clinical, and translational medical research. JIM publishes on all topics and specialty areas that are critical to the conduct of the entire spectrum of biomedical research: from the translation of clinical observations at the bedside, to basic and animal research to clinical research and the implementation of innovative medical care.
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