Pathogenic Roles of CD14, Galectin-3, and OX40 during Experimental Cerebral Malaria in Mice

摘要: An in-depth knowledge of the host molecules and biological pathways that contribute towards pathogenesis cerebral malaria would help guide development novel prognostics therapeutics. Genome-wide transcriptional profiling brain tissue during experimental (ECM ) caused by Plasmodium berghei ANKA parasites in mice, a well established surrogate human malaria, has been useful predicting functional classes genes involved altered course disease. To further understand contribution individual to ECM, we examined relevance three – CD14, galectin-3, OX40 were previously shown be overexpressed ECM. We find CD14 plays predominant role induction ECM regulation parasite density; deletion gene not only prevented onset disease majority susceptible mice (only 21% CD14-deficient compared 80% wildtype developed p<0.0004) but also had an ameliorating effect on parasitemia (a 2 fold reduction phase). Furthermore, galectin-3 C57BL/6 resulted partial protection from (47% galectin-3-deficient versus 93% p<0.0073). Subsequent adherence assays suggest induced is mediated recognition binding P. parasites. A previous study demonstrated infiltrating T cells are strongly activated CD44+CD62L− differentiated memory [1]. OX40, marker both cell activation memory, selectively upregulated its distribution among CD4+ CD8+ accumulated vasculature approximately equal.