ArticlePLoS pathogens2015
Perivascular Arrest of CD8+ T Cells Is a Signature of Experimental Cerebral Malaria.
Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Experimental procedures for flow cytometry of wild-type mouse brain: a systematic review.Frontiers in immunology · 2023Pooled it
- CD8+ T cells target cerebrovasculature in children with cerebral malaria.The Journal of clinical investigation · 2020Trial
- CXCL10CNS neuroscience & therapeutics · 2025Article
- The spatiotemporal transcriptional profiling of murine brain during cerebral malaria progression and after artemisinin treatment.Nature communications · 2025Article
- Effects of nanocapsules containing lumefantrine and artemether in an experimental model of cerebral malaria.Discover nano · 2024Article
- CD8CNS neuroscience & therapeutics · 2024Article
- Single cell RNA sequencing reveals endothelial cell killing and resolution pathways in experimental malaria-associated acute respiratory distress syndrome.PLoS pathogens · 2024Article
- Unravelling mysteries at the perivascular space: a new rationale for cerebral malaria pathogenesis.Trends in parasitology · 2024Review
- Pathogenetic mechanisms and treatment targets in cerebral malaria.Nature reviews. Neurology · 2023Review
- The deubiquitinating enzyme OTUD7b protects dendritic cells from TNF-induced apoptosis by stabilizing the E3 ligase TRAF2.Cell death & disease · 2023Article
- In vitro model of brain endothelial cell barrier reveals alterations induced by Plasmodium blood stage factors.Parasitology research · 2023Article
- The IL-33/ST2 Pathway in Cerebral Malaria.International journal of molecular sciences · 2022Review
- Neurofilament light chain plasma levels are associated with area of brain damage in experimental cerebral malaria.Scientific reports · 2022Article
- Autophagy Pathways in the Genesis ofLife (Basel, Switzerland) · 2022Article
- Immune dynamics in the CNS and its barriers during homeostasis and disease.Immunological reviews · 2022Review
- The immunomodulatory effect of microglia on ECM neuroinflammation via the PD-1/PD-L1 pathway.CNS neuroscience & therapeutics · 2022Article
- Suppression of Plasmodium MIF-CD74 signaling protects against severe malaria.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Memory CD8Immunology · 2021Article
- CD47 blockade reduces the pathologic features of experimental cerebral malaria and promotes survival of hosts withProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Attenuated T Cell Responses Are Associated With the Blockade of Cerebral Malaria Development by YOP1-DeficientFrontiers in immunology · 2021Article
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 3 countries.
Funding
Abstract
There is significant evidence that brain-infiltrating CD8+ T cells play a central role in the development of experimental cerebral malaria (ECM) during Plasmodium berghei ANKA infection of C57BL/6 mice. However, the mechanisms through which they mediate their pathogenic activity during malaria infection remain poorly understood. Utilizing intravital two-photon microscopy combined with detailed ex vivo flow cytometric analysis, we show that brain-infiltrating T cells accumulate within the perivascular spaces of brains of mice infected with both ECM-inducing (P. berghei ANKA) and non-inducing (P. berghei NK65) infections. However, perivascular T cells displayed an arrested behavior specifically during P. berghei ANKA infection, despite the brain-accumulating CD8+ T cells exhibiting comparable activation phenotypes during both infections. We observed T cells forming long-term cognate interactions with CX3CR1-bearing antigen presenting cells within the brains during P. berghei ANKA infection, but abrogation of this interaction by targeted depletion of the APC cells failed to prevent ECM development. Pathogenic CD8+ T cells were found to colocalize with rare apoptotic cells expressing CD31, a marker of endothelial cells, within the brain during ECM. However, cellular apoptosis was a rare event and did not result in loss of cerebral vasculature or correspond with the extensive disruption to its integrity observed during ECM. In summary, our data show that the arrest of T cells in the perivascular compartments of the brain is a unique signature of ECM-inducing malaria infection and implies an important role for this event in the development of the ECM-syndrome.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.