Transcriptomic profiling of microglia reveals signatures of cell activation and immune response, during experimental cerebral malaria
Abstract
Cerebral malaria is a pathology involving inflammation in the brain. There are many immune cell types activated during this process, but there is little information on the response of microglia, in this severe complication. We examined microglia by genome wide transcriptomic analysis in a model of experimental cerebral malaria (ECM), in which C57BL/6 mice are infected with Plasmodium berghei ANKA. Thousands of transcripts were differentially expressed in microglia at two different time points during infection. Proliferation of microglia was a dominant feature before the onset of ECM, and supporting this, we observed an increase in numbers of these cells in the brain. When cerebral malaria symptoms were manifest, genes involved in immune responses and chemokine production were upregulated, which were possibly driven by Type I Interferon. Consistent with this hypothesis, in vitro culture of a microglial cell line with Interferon-β, but not infected red blood cells, resulted in production of several of the chemokines shown to be upregulated in the gene expression analysis. It appears that these responses are associated with ECM, as microglia from mice infected with a mutant P. berghei parasite (ΔDPAP3), which does not cause ECM, did not show the same level of activation or proliferation.
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BIRC5 has been previously characterised as highly expressed by proliferating microglia during development and in response to injury.
“BIRC5 has been previously characterised as highly expressed by proliferating microglia during development and in response to injury66.”
From Mouse microglia express unique miRNA-mRNA networks to facilitate age-specific functions in the developing central nervous system (2023) · cites this paper as [66]
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Walsh, A. D., Stone, S., Freytag, S., Aprico, A., Kilpatrick, T. J., Ansell, B. R. E., & Binder, M. D. (2023) · Communications Biology · doi:10.1038/s42003-023-04926-8 · Cited by 9 · see citing works
- Authors
- Capuccini, B., Lin, J., Talavera-López, C., Khan, S. M., Sodenkamp, J., Spaccapelo, R., & Langhorne, J.
- Venue
- Scientific Reports
- Published
- 2016-12-19
- Volume
- 6
- Issue
- 1
- ISSN
- 2045-2322
- PMC
- PMC5171943
- Cited by
- 52
- References
- 3
- Language
- en
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