Abstract
Cerebral malaria (CM) is a major complication of Plasmodium falciparum infection in children. The pathogenesis of CM involves vascular inflammation, immune stimulation, and obstruction of cerebral capillaries. Platelets have a prominent role in both immune responses and vascular obstruction. We now demonstrate that the platelet-derived chemokine, platelet factor 4 (PF4)/CXCL4, promotes the development of experimental cerebral malaria (ECM). Plasmodium-infected red blood cells (RBCs) activated platelets independently of vascular effects, resulting in increased plasma PF4. PF4 or chemokine receptor CXCR3 null mice had less severe ECM, including decreased T cell recruitment to the brain, and platelet depletion or aspirin treatment reduced the development of ECM. We conclude that Plasmodium-infected RBCs can directly activate platelets, and platelet-derived PF4 then contributes to immune activation and T cell trafficking as part of the pathogenesis of ECM.
Original language | English (US) |
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Pages (from-to) | 179-187 |
Number of pages | 9 |
Journal | Cell Host and Microbe |
Volume | 4 |
Issue number | 2 |
DOIs | |
State | Published - Aug 14 2008 |
Keywords
- CELLBIO
- CELLIMMUNO
- MICROBIO
ASJC Scopus subject areas
- Parasitology
- Microbiology
- Virology