<it>Plasmodium yoelii </it>17XL infection up-regulates RANTES, CCR1, CCR3 and CCR5 expression, and induces ultrastructural changes in the cerebellum
<p>Abstract</p> <p>Background</p> <p>Malaria 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 cytok...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2005-12-01
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| Series: | Malaria Journal |
| Online Access: | http://www.malariajournal.com/content/4/1/63 |
| _version_ | 1818859303233126400 |
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| author | Singh Shailesh Olver Christine S Adjei Andrew A Irune Ikovwaiza Armah Henry B Sarfo Bismark Y Lillard James W Stiles Jonathan K |
| author_facet | Singh Shailesh Olver Christine S Adjei Andrew A Irune Ikovwaiza Armah Henry B Sarfo Bismark Y Lillard James W Stiles Jonathan K |
| author_sort | Singh Shailesh |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Malaria 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 <it>Plasmodium</it>-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.</p> <p>Methods</p> <p>The alterations in immunomodulator gene expression in brains of <it>Plasmodium yoelii </it>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.</p> <p>Results</p> <p>RANTES (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.</p> <p>Conclusion</p> <p>The upregulation of RANTES, CCR1, CCR3, and CCR5 mRNA, and RANTES protein mediate inflammation and cellular degradation in the cerebellum during <it>P. yoelii </it>17XL malaria.</p> |
| first_indexed | 2024-12-19T09:10:02Z |
| format | Article |
| id | doaj.art-a1d8e19e446d4b1f8abddd87d53c9eeb |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-19T09:10:02Z |
| publishDate | 2005-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-a1d8e19e446d4b1f8abddd87d53c9eeb2022-12-21T20:28:14ZengBMCMalaria Journal1475-28752005-12-01416310.1186/1475-2875-4-63<it>Plasmodium yoelii </it>17XL infection up-regulates RANTES, CCR1, CCR3 and CCR5 expression, and induces ultrastructural changes in the cerebellumSingh ShaileshOlver Christine SAdjei Andrew AIrune IkovwaizaArmah Henry BSarfo Bismark YLillard James WStiles Jonathan K<p>Abstract</p> <p>Background</p> <p>Malaria 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 <it>Plasmodium</it>-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.</p> <p>Methods</p> <p>The alterations in immunomodulator gene expression in brains of <it>Plasmodium yoelii </it>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.</p> <p>Results</p> <p>RANTES (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.</p> <p>Conclusion</p> <p>The upregulation of RANTES, CCR1, CCR3, and CCR5 mRNA, and RANTES protein mediate inflammation and cellular degradation in the cerebellum during <it>P. yoelii </it>17XL malaria.</p>http://www.malariajournal.com/content/4/1/63 |
| spellingShingle | Singh Shailesh Olver Christine S Adjei Andrew A Irune Ikovwaiza Armah Henry B Sarfo Bismark Y Lillard James W Stiles Jonathan K <it>Plasmodium yoelii </it>17XL infection up-regulates RANTES, CCR1, CCR3 and CCR5 expression, and induces ultrastructural changes in the cerebellum Malaria Journal |
| title | <it>Plasmodium yoelii </it>17XL infection up-regulates RANTES, CCR1, CCR3 and CCR5 expression, and induces ultrastructural changes in the cerebellum |
| title_full | <it>Plasmodium yoelii </it>17XL infection up-regulates RANTES, CCR1, CCR3 and CCR5 expression, and induces ultrastructural changes in the cerebellum |
| title_fullStr | <it>Plasmodium yoelii </it>17XL infection up-regulates RANTES, CCR1, CCR3 and CCR5 expression, and induces ultrastructural changes in the cerebellum |
| title_full_unstemmed | <it>Plasmodium yoelii </it>17XL infection up-regulates RANTES, CCR1, CCR3 and CCR5 expression, and induces ultrastructural changes in the cerebellum |
| title_short | <it>Plasmodium yoelii </it>17XL infection up-regulates RANTES, CCR1, CCR3 and CCR5 expression, and induces ultrastructural changes in the cerebellum |
| title_sort | it plasmodium yoelii it 17xl infection up regulates rantes ccr1 ccr3 and ccr5 expression and induces ultrastructural changes in the cerebellum |
| url | http://www.malariajournal.com/content/4/1/63 |
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