Protein kinase C-theta is required for development of experimental cerebral malaria.

Abstract : Cerebral malaria is the most severe neurologic complication in children and young adults infected with Plasmodium falciparum. T-cell activation is required for development of Plasmodium berghei ANKA (PbA)-induced experimental cerebral malaria (CM). To characterize the T-cell activation pathway involved, the role of protein kinase C-theta (PKC-θ) in experimental CM development was examined. PKC-θ-deficient mice are resistant to CM development. In the absence of PKC-θ, no neurologic sign of CM developed after blood stage PbA infection. Resistance of PKC-θ-deficient mice correlated with unaltered cerebral microcirculation and absence of ischemia, as documented by magnetic resonance imaging and magnetic resonance angiography, whereas wild-type mice developed distinct microvascular pathology. Recruitment and activation of CD8(+) T cells, and ICAM-1 and CD69 expression were reduced in the brain of resistant mice; however, the pulmonary inflammation and edema associated with PbA infection were still present in the absence of functional PKC-θ. Resistant PKC-θ-deficient mice developed high parasitemia, and died at 3 weeks with severe anemia. Therefore, PKC-θ signaling is crucial for recruitment of CD8(+) T cells and development of brain microvascular pathology resulting in fatal experimental CM, and may represent a novel therapeutic target of CM.
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Submitted on : Tuesday, May 10, 2011 - 2:45:55 PM
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Mathilde Fauconnier, Marie-Laure Bourigault, Sandra Meme, Frederic Szeremeta, Jennifer Palomo, et al.. Protein kinase C-theta is required for development of experimental cerebral malaria.. American Journal of Pathology, American Society for Investigative Pathology, 2011, 178 (1), pp.212-21. ⟨10.1016/j.ajpath.2010.11.008⟩. ⟨hal-00591910⟩



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