ORIGINAL RESEARCH article
Front. Immunol.
Sec. Molecular Innate Immunity
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1494418
This article is part of the Research TopicExploring Microglial Diversity and Its Impact on Neurological DiseasesView all 3 articles
Microglia exhibit a dynamic response, modulating inducible nitric oxide synthase expression and the production pro-inflammatory cytokines during experimental cerebral malaria
Provisionally accepted
Lucas Freire-Antunes1,2
Uyla Ornellas-Garcia1,2
Marcos Vinícius Rangel-Ferreira1,2Mônica Lucas Ribeiro-Almeida1,2
Leonardo Jose de Moura Carvalho1,2Cláudio Tadeu Daniel-Ribeiro1,2
Flávia Lima Ribeiro-Gomes1,2*- 1Laboratório de Pesquisa em Malária, Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Rio de Janeiro, Brazil
- 2Centro 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, Rio de Janeiro, Brazil
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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 (Plasmodium berghei 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 (CD45 hi CD11b -CD3 + cells), inflammatory monocytes (CD45 hi CD11b + TMEM119 -CD206 -cells), resident macrophages (CD45 hi CD11b + TMEM119 -CD206 + cells), and microglia (CD45 low CD11b + TMEM119 + CD206 -cells) following infection. Moreover, our ex vivo 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.
Keywords: experimental cerebral malaria, Macrophages, Malaria, Microglia, Nitric Oxide, IL-1β, iNOS, TNF
Received: 10 Sep 2024; Accepted: 08 Jul 2025.
Copyright: © 2025 Freire-Antunes, Ornellas-Garcia, Rangel-Ferreira, Ribeiro-Almeida, Carvalho, Daniel-Ribeiro and Ribeiro-Gomes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Flávia Lima Ribeiro-Gomes, Laboratório de Pesquisa em Malária, Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, 21040-900, Rio de Janeiro, Brazil
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