title: Host response to cytoadherence in Plasmodium falciparum.
abstract: Cytoadherence of PRBCs (Plasmodium falciparum-infected red blood cells) to host endothelium has been associated with pathology in severe malaria, but, despite extensive information on the primary processes involved in the adhesive interactions, the mechanisms underlying the disease are poorly understood. Endothelial cells have the ability to mobilize immune and pro-adhesive responses when exposed to both PRBCs and TNF (tumour necrosis factor). In addition, there is also an up-regulation by PRBCs and TNF and a concurrent down-regulation of a range of genes involved in inflammation and cell death, by PRBCs and TNF. We propose that the balance between positive and negative regulation will contribute to endothelial pathology during malarial infection. Apposition of PRBCs has been shown by a number of groups to activate signalling pathways. This is dependent, at least in part, on the cytoadherence characteristics of the invading isolate, such that the avidity of the PRBC for the receptor on host endothelium is proportional to the level of activation of the signalling pathways. An understanding of the post-adhesive processes produced by cytoadherence may help us to understand the variable pathology seen in malaria and to design appropriate therapies to alleviate severe disease.
authors: Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.
authors: Srabasti J
authors: SJ
authors: Chakravorty
authors: Katie R
authors: KR
authors: Hughes
authors: Alister G
authors: AG
authors: Craig
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D042783:Endothelial Cells / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology; D006790:Host-Parasite Interactions; D006801:Humans; D016778:Malaria, Falciparum / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D048069:Tumor Necrosis Factors / Q000276:immunology
chemical_list: D048069:Tumor Necrosis Factors