Freire-Antunes Lucas, Ornellas-Garcia Uyla, Rangel-Ferreira Marcos, Ribeiro-Almeida Mônica Lucas, Carvalho Leonardo José Moura, Daniel-Ribeiro Cláudio Tadeu, Ribeiro-Gomes Flávia Lima
Laboratório de Pesquisa em Malária, Instituto Oswaldo Cruz and Centro de Pesquisa, Diagnóstico e Treinamento em Malária (CPD-Mal) of Fundação Oswaldo Cruz (Fiocruz) and of Secretaria de Vigilância em Saúde (SVS), Ministério da Saúde, Rio de Janeiro, Brazil.
Front Immunol. 2025 Jul 23;16:1494418. doi: 10.3389/fimmu.2025.1494418. eCollection 2025.
Microglia play a fundamental role in maintaining central nervous system homeostasis by monitoring brain tissue for physical, structural, and biochemical alterations. Its involvement in the pathogenesis of various neurological disorders is well documented. However, the role of microglia in cerebral malaria, a disease associated with high mortality and long-term neurological sequelae, remains poorly understood. In this study, we utilized the classical model of experimental cerebral malaria ( ANKA-infected C57BL/6 mice) to investigate the dynamics and response of resident brain cell populations, particularly microglia, and the influx of other leukocytes during the development of experimental cerebral malaria. By employing flow cytometry and established markers for different leukocyte populations, we were able to discern and document an increase in the number of Ly6C T cells (CD45CD11bCD3 cells), inflammatory monocytes (CD45CD11bTMEM119CD206 cells), resident macrophages (CD45CD11bTMEM119CD206 cells), and microglia (CD45CD11b TMEM119CD206 cells) following infection. Moreover, our analysis demonstrated an increment in the overall number of inflammatory monocytes, resident macrophages and microglia expressing inducible nitric oxide synthase (iNOS), in addition to those producing interleukin-1β or TNF. These findings highlight the pronounced reactivity of microglia in experimental cerebral malaria and provide valuable information on cell dynamics and immune responses in the brain.
小胶质细胞通过监测脑组织的物理、结构和生化改变,在维持中枢神经系统稳态中发挥着重要作用。其在各种神经疾病发病机制中的作用已有充分记录。然而,小胶质细胞在脑型疟疾(一种与高死亡率和长期神经后遗症相关的疾病)中的作用仍知之甚少。在本研究中,我们利用实验性脑型疟疾的经典模型(感染ANKA的C57BL/6小鼠)来研究实验性脑型疟疾发展过程中脑内常驻细胞群体,特别是小胶质细胞的动态变化和反应,以及其他白细胞的流入情况。通过使用流式细胞术和针对不同白细胞群体的既定标志物,我们能够识别并记录感染后Ly6C T细胞(CD45CD11bCD3细胞)、炎性单核细胞(CD45CD11bTMEM119CD206细胞)、常驻巨噬细胞(CD45CD11bTMEM119CD206细胞)和小胶质细胞(CD45CD11b TMEM119CD206细胞)数量的增加。此外,我们的分析表明,除了产生白细胞介素-1β或肿瘤坏死因子的细胞外,表达诱导型一氧化氮合酶(iNOS)的炎性单核细胞、常驻巨噬细胞和小胶质细胞的总数也有所增加。这些发现突出了小胶质细胞在实验性脑型疟疾中的显著反应性,并为脑中的细胞动态变化和免疫反应提供了有价值的信息。