title: 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.
authors.affiliation: The Francis Crick Institute, London NW1 1AT, UK.
authors.forename: Barbara
authors.initials: B
authors.lastname: Capuccini
authors.affiliation: The Francis Crick Institute, London NW1 1AT, UK.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Lin
authors.affiliation: The Francis Crick Institute, London NW1 1AT, UK.
authors.forename: Carlos
authors.initials: C
authors.lastname: Talavera-López
authors.affiliation: Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, Netherlands.
authors.forename: Shahid M
authors.initials: SM
authors.lastname: Khan
authors.affiliation: The Francis Crick Institute, London NW1 1AT, UK.
authors.forename: Jan
authors.initials: J
authors.lastname: Sodenkamp
authors.affiliation: Department of Experimental Medicine, University of Perugia, 06132 Perugia, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Spaccapelo
authors.affiliation: The Francis Crick Institute, London NW1 1AT, UK.
authors.forename: Jean
authors.initials: J
authors.lastname: Langhorne
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D016000:Cluster Analysis; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D005260:Female; D020869:Gene Expression Profiling; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D050839:Interferon Regulatory Factor-7 / Q000235:genetics / Q000378:metabolism; D007370:Interferon Type I / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism; D016779:Malaria, Cerebral / Q000276:immunology / Q000469:parasitology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010962:Plasmodium berghei / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity; D025341:Principal Component Analysis; D015854:Up-Regulation
chemical_list: D018925:Chemokines; D015395:Histocompatibility Antigens Class I; D050839:Interferon Regulatory Factor-7; D007370:Interferon Type I; C494235:Irf7 protein, mouse; D016899:Interferon-beta; C475083:Oasl1 protein, mouse; D015088:2',5'-Oligoadenylate Synthetase