Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Malaria primes the innate immune response due to IFNg induced enhancement of Toll-like receptor expression and function.


ABSTRACT: Patients with febrile malaria were recruited in order to determine Peripheral Blood Mononuclear Cell (PBMC) gene expression during malaria. Blood was harvested from patients during the acute phase of the illness, and then patients were given a curative regimen of antimalarials. Three to four weeks after treatment, patients returned to the malaria clinic and blood was collected again, in order that each patient could serve as his or her own control. PBMC were isolated at the time of blood collection and forzen in RNA extraction buffer. At the end of the study, each patient was arrayed for ~47,000 transcripts, comparing gene expression at the end of therapy to that at the beginning. The goal was to determine which genes were altered as a result of disease at least 2 fold in a statistically significant manner and to assess if the genes involved could be related to Toll-like receptor signaling pathways. Approximately 60 genes involved in inflammation were confirmed by qPCR. Gene expression profiles of blood cells from 14 individuals with malaria are compared to gene expression in blood cells from the same 14 individuals medicated and recovered from malaria symptoms (28 arrays in total).

ORGANISM(S): Homo sapiens

SUBMITTER: Harry Björkbacka 

PROVIDER: E-GEOD-15221 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Malaria primes the innate immune response due to interferon-gamma induced enhancement of toll-like receptor expression and function.

Franklin Bernardo S BS   Parroche Peggy P   Ataíde Marco Antonio MA   Lauw Fanny F   Ropert Catherine C   de Oliveira Rosane B RB   Pereira Dhelio D   Tada Mauro Shugiro MS   Nogueira Paulo P   da Silva Luiz Hildebrando Pereira LH   Bjorkbacka Harry H   Golenbock Douglas T DT   Gazzinelli Ricardo T RT  

Proceedings of the National Academy of Sciences of the United States of America 20090318 14


Malaria-induced sepsis is associated with an intense proinflammatory cytokinemia for which the underlying mechanisms are poorly understood. It has been demonstrated that experimental infection of humans with Plasmodium falciparum primes Toll-like receptor (TLR)-mediated proinflammatory responses. Nevertheless, the relevance of this phenomenon during natural infection and, more importantly, the mechanisms by which malaria mediates TLR hyperresponsiveness are unclear. Here we show that TLR respons  ...[more]

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