| First Author | Fauconnier M | Year | 2011 |
| Journal | Am J Pathol | Volume | 178 |
| Issue | 1 | Pages | 212-21 |
| PubMed ID | 21224058 | Mgi Jnum | J:168090 |
| Mgi Id | MGI:4881866 | Doi | 10.1016/j.ajpath.2010.11.008 |
| Citation | Fauconnier M, et al. (2011) Protein kinase C-theta is required for development of experimental cerebral malaria. Am J Pathol 178(1):212-21 |
| abstractText | 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-theta) in experimental CM development was examined. PKC-theta-deficient mice are resistant to CM development. In the absence of PKC-theta, no neurologic sign of CM developed after blood stage PbA infection. Resistance of PKC-theta-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-theta. Resistant PKC-theta-deficient mice developed high parasitemia, and died at 3 weeks with severe anemia. Therefore, PKC-theta 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. |
