Production, Fate and Pathogenicity of Plasma Microparticles in Murine Cerebral Malaria
Cerebral malaria (CM) is a potentially fatal neurological syndrome characterised by unrousable coma. Since the detection of high levels of plasma microparticles (MP) in patients with CM, it has been demonstrated that inhibition of MP production confers protection from murine CM. However, the precise mechanisms of action of these MP during CM have not been completely deciphered. In this study, we used experimental models of CM to measure the production and origins of MP over the course of infection. We found low baseline circulating MP in healthy mice and these were subsequently raised at the time of the neurological syndrome. Phenotypic analyses showed that circulating MP were predominantly from activated host cells that have previously been established to participate in CM pathogenesis. We show for the first time transferred MP impairing endothelial integrity and inducing CM-like pathology in the brain and lung of healthy animals. Our study dissects what tissues these MP localise to exert their effects, as little is known about their fate following the initial release. These data suggest a causal relationship between MP and the development of CM and also warrant further investigation into the representation of MP as a marker of CM risk.
Vyšlo v časopise:
Production, Fate and Pathogenicity of Plasma Microparticles in Murine Cerebral Malaria. PLoS Pathog 10(3): e32767. doi:10.1371/journal.ppat.1003839
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1003839
Souhrn
Cerebral malaria (CM) is a potentially fatal neurological syndrome characterised by unrousable coma. Since the detection of high levels of plasma microparticles (MP) in patients with CM, it has been demonstrated that inhibition of MP production confers protection from murine CM. However, the precise mechanisms of action of these MP during CM have not been completely deciphered. In this study, we used experimental models of CM to measure the production and origins of MP over the course of infection. We found low baseline circulating MP in healthy mice and these were subsequently raised at the time of the neurological syndrome. Phenotypic analyses showed that circulating MP were predominantly from activated host cells that have previously been established to participate in CM pathogenesis. We show for the first time transferred MP impairing endothelial integrity and inducing CM-like pathology in the brain and lung of healthy animals. Our study dissects what tissues these MP localise to exert their effects, as little is known about their fate following the initial release. These data suggest a causal relationship between MP and the development of CM and also warrant further investigation into the representation of MP as a marker of CM risk.
Zdroje
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Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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