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The role of monocytes in the pathology of severe malaria.

$231,850U19FY2012AINIH

Michigan State University, East Lansing MI

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Abstract

Severe malaria (SM) places a disproportionate burden of nriortality and death on the children of Sub-Saharan Africa. Death, as a result of SM, is not a direct consequence of parasite load but is associated with excessive inflammatory response(s) in the brain and lungs of SM patients. Parasite-derived activators of the innate immune response, together with inflammatory monocytes, have been implicated in mediating this tissue damage. However, the activation pathways responsible for localized inflammation and compromising the blood brain barrier (BBB) remain to be determined. We propose elucidating the mechanism(s) by: 1. Defining the transcriptional profiles at the sites of damage in tissues from pediatric SM. We propose assembling a transcriptional

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