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Updated: Jun 19, 2026
Isolation and Analysis of Brain-sequestered Leukocytes from Plasmodium berghei ANKA-infected Mice
Published on: January 2, 2013
CXCL10highTNFαhighKi67+ Microglia Recruit and Activate CD8+ T Cells in the Brainstem During Experimental Cerebral
Yi Wang1, Jiao Liang1, Chao Yang2
1Department of Medical Microbiology and Parasitology, Air Force Medical University, Xi'an, Shaanxi, China.
Aims:
This study aimed to investigate the heterogeneity of microglia and their role in recruiting and activating CD8+ T cells in experimental cerebral malaria (ECM).
Methods:
C57BL/6J mice were infected with Plasmodium berghei ANKA (PbA) to induce ECM. Morphology and distribution of microglia were assessed via immunofluorescence (IF) staining and electron microscopy. Single-cell RNA-sequencing (scRNA-seq) analyzed the activation characteristics of infiltrating CD8+ T cells and the transcriptional heterogeneity of microglia in ECM. In vitro, ECM-associated microglia were induced by TNFα, IFNγ, and parasite-infected red blood cells (pRBCs). The interaction between microglia and CD8+ T cells was explored in co-culture systems through transwell assay, adhesion assay, and cytotoxicity test.
Results:
In vivo, microglia were aggregated in the brainstem and olfactory bulb in the ECM brain, regions that exhibited more severe pathological injury. The transcriptional characteristics of ECM microglia distinguished from physiological microglia and exhibit morphological heterogeneity in the ECM brain. Infiltrating CD8+ T cells in the ECM brainstem exhibit sustained activation characteristics associated with microglia interaction. Based on subcluster analysis, a unique subtype of ECM-associated microglia was identified, characterized by CXCL10highTNFαhighKi67+. These microglia mediated the recruitment and sustained activation of CD8+ T cells through persistent interactions in co-culture systems.
Conclusions:
Our study identified an ECM-associated microglia subtype and explored its interaction with CD8+ T cells, which deepened the understanding of the multifaceted role of microglia in the pathogenesis of CM neuroinflammation.
Insights
Researchers identified a specific subtype of microglia that recruits and activates CD8+ T cells in experimental cerebral malaria (ECM), advancing understanding of neuroinflammation in this condition.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Experimental cerebral malaria (ECM) is a severe neurological complication of Plasmodium infection.
- Microglia, the resident immune cells of the brain, play a critical role in neuroinflammation.
- The heterogeneity and specific functions of microglia in ECM pathogenesis remain incompletely understood.
Purpose of the Study:
- To investigate the heterogeneity of microglia in ECM.
- To elucidate the role of microglia in recruiting and activating CD8+ T cells during ECM.
- To identify specific microglia subtypes involved in ECM-associated neuroinflammation.
Main Methods:
- Induction of ECM in C57BL/6J mice using Plasmodium berghei ANKA (PbA).
- Assessment of microglia morphology and distribution using immunofluorescence and electron microscopy.
- Single-cell RNA-sequencing (scRNA-seq) to analyze microglia and CD8+ T cell transcriptional profiles.
- In vitro induction of ECM-associated microglia and co-culture systems to study microglia-T cell interactions.
Main Results:
- Microglia aggregated in brain regions with severe pathological injury in ECM.
- Transcriptional and morphological heterogeneity of microglia was observed in the ECM brain.
- A unique ECM-associated microglia subtype (CXCL10highTNFαhighKi67+) was identified.
- These microglia were found to mediate CD8+ T cell recruitment and sustained activation via persistent interactions.
Conclusions:
- Identification of a novel ECM-associated microglia subtype.
- Demonstration of this microglia subtype's role in recruiting and activating CD8+ T cells.
- Enhanced understanding of microglia's complex role in CM neuroinflammation pathogenesis.
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