Activated Neutrophils Are Associated with Pediatric Cerebral Malaria Vasculopathy in Malawian Children

MBio
Catherine Manix FeintuchJohanna P Daily

Abstract

Most patients with cerebral malaria (CM) sustain cerebral microvascular sequestration of Plasmodium falciparum-infected red blood cells (iRBCs). Although many young children are infected with P. falciparum, CM remains a rare outcome; thus, we hypothesized that specific host conditions facilitate iRBC cerebral sequestration. To identify these host factors, we compared the peripheral whole-blood transcriptomes of Malawian children with iRBC cerebral sequestration, identified as malarial-retinopathy-positive CM (Ret+CM), to the transcriptomes of children with CM and no cerebral iRBC sequestration, defined as malarial-retinopathy-negative CM (Ret-CM). Ret+CM was associated with upregulation of 103 gene set pathways, including cytokine, blood coagulation, and extracellular matrix (ECM) pathways (P < 0.01; false-discovery rate [FDR] of <0.05). Neutrophil transcripts were the most highly upregulated individual transcripts in Ret+CM patients. Activated neutrophils can modulate diverse host processes, including the ECM, inflammation, and platelet biology to potentially facilitate parasite sequestration. Therefore, we compared plasma neutrophil proteins and neutrophil chemotaxis between Ret+CM and Ret-CM patients. Plasma levels of human ...Continue Reading

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Citations

Jan 19, 2018·Journal of Leukocyte Biology·Tatiana A PáduaMaria G Henriques
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Methods Mentioned

BETA
confocal microscopy
reverse transcription-PCR
enzyme-linked immunosorbent assay
ELISA
genotyping

Software Mentioned

Gene Set Enrichment Analysis ( GSEA )
dChip
GenePattern
Ingenuity Pathway Analysis
Slidebook
CateGOrizer tool Pathway Analysis ( IPA )
GSEA
CateGOrizer
Ingenuity Pathway Analysis ( IPA )

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