title: Cerebral malaria protection in mice by species-specific Plasmodium coinfection is associated with reduced CC chemokine levels in the brain.
abstract: Cerebral malaria is a major pathological complication of Plasmodium falciparum infection in humans. Epidemiological observations have suggested that the clinical evolution of P. falciparum infections may be influenced by the concurrent presence of another Plasmodium species. Infection of susceptible mouse strains with P. berghei ANKA (PbA) provides an experimental model of cerebral malaria which has been extensively used to identify different components of the immune system involved in cerebral malaria. This model has also been employed to investigate the influence of experimental mixed-Plasmodium-species infections on the expression of cerebral malaria; PbA-induced cerebral malaria is completely inhibited by the simultaneous presence of P. yoelii yoelii 17 X clone 1.1 parasites, and accumulation of CD8(+) T cells in the brain vasculature is abolished. We investigated whether brain levels of CD8(+) -T-cell-chemoattractant chemokines CCL3, CCL4 and CCL5 are reduced in these protected coinfected mice compared with PbA-infected mice. Coinfected mice were found to exhibit significantly reduced levels of all three chemokines on day 6 post-infection. This finding may contribute to the abolition of the accumulation of CD8(+) T cells in the brain vasculature and the prevention of the development of cerebral malaria in coinfected mice.
authors.affiliation: Infection & Immunity, Faculty of Biomedical & Life Sciences, University of Glasgow, Glasgow, Scotland, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Clark
authors.forename: R S
authors.initials: RS
authors.lastname: Phillips
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D054405:Chemokine CCL3 / Q000096:biosynthesis; D054407:Chemokine CCL4 / Q000096:biosynthesis; D018946:Chemokine CCL5 / Q000096:biosynthesis; D019742:Chemokines, CC / Q000378:metabolism*; D060085:Coinfection; D005260:Female; D016779:Malaria, Cerebral / Q000276:immunology* / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D010962:Plasmodium berghei; D010967:Plasmodium yoelii; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: C496534:Ccl3 protein, mouse; C503460:Ccl5 protein, mouse; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019742:Chemokines, CC; D012333:RNA, Messenger