Plasmodium yoelii 17XL infection up-regulates RANTES, CCR1, CCR3 and CCR5 expression, and induces ultrastructural changes in the cerebellumReportar como inadecuado

Plasmodium yoelii 17XL infection up-regulates RANTES, CCR1, CCR3 and CCR5 expression, and induces ultrastructural changes in the cerebellum - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Malaria Journal

, 4:63

First Online: 16 December 2005Received: 23 August 2005Accepted: 16 December 2005


BackgroundMalaria afflicts 300–500 million people causing over 1 million deaths globally per year. The immunopathogenesis of malaria is mediated partly by co mplex cellular and immunomodulator interactions involving co-regulators such as cytokines and adhesion molecules. However, the role of chemokines and their receptors in malaria immunopathology remains unclear. RANTES Regulated on Activation Normal T-Cell Expressed and Secreted is a chemokine involved in the generation of inflammatory infiltrates. Recent studies indicate that the degradation of cell-cell junctions, blood-brain barrier dysfunction, recruitment of leukocytes and Plasmodium-infected erythrocytes into and occlusion of microvessels relevant to malaria pathogenesis are associated with RANTES expression. Additionally, activated lymphocytes, platelets and endothelial cells release large quantities of RANTES, thus suggesting a unique role for RANTES in the generation and maintenance of the malaria-induced inflammatory response. The hypothesis of this study is that RANTES and its corresponding receptors CCR1, CCR3 and CCR5 modulate malaria immunopathogenesis. A murine malaria model was utilized to evaluate the role of this chemokine and its receptors in malaria.

MethodsThe alterations in immunomodulator gene expression in brains of Plasmodium yoelii 17XL-infected mice was analysed using cDNA microarray screening, followed by a temporal comparison of mRNA and protein expression of RANTES and its corresponding receptors by qRT-PCR and Western blot analysis, respectively. Plasma RANTES levels was determined by ELISA and ultrastructural studies of brain sections from infected and uninfected mice was conducted.

ResultsRANTES p < 0.002, CCR1 p < 0.036, CCR3 p < 0.033, and CCR5 p < 0.026 mRNA were significantly upregulated at peak parasitaemia and remained high thereafter in the experimental mouse model. RANTES protein in the brain of infected mice was upregulated p < 0.034 compared with controls. RANTES plasma levels were significantly upregulated; two to three fold in infected mice compared with controls p < 0.026. Some d istal microvascular endothelium in infected cerebellum appeared degraded, but remained intact in controls.

ConclusionThe upregulation of RANTES, CCR1, CCR3, and CCR5 mRNA, and RANTES protein mediate inflammation and cellular degradation in the cerebellum during P. yoelii 17XL malaria.

List of abbreviations usedBBBBlood-Brain Barrier

CMcerebral malaria

ECMexperimental cerebral malaria

MEmicrovascular endothelium

NCMnon-cerebral malaria

RBCred blood cell

WBCwhite blood cell

TNFTumor Necrosis Factor



Electronic supplementary materialThe online version of this article doi:10.1186-1475-2875-4-63 contains supplementary material, which is available to authorized users.

Download fulltext PDF

Autor: Bismark Y Sarfo - Henry B Armah - Ikovwaiza Irune - Andrew A Adjei - Christine S Olver - Shailesh Singh - James W Lill


Documentos relacionados