Differential regulation of beta-chemokines in children with Plasmodium falciparum malaria.

Published

Journal Article

Chemokines regulate the host immune response to a variety of infectious pathogens. Since the role of chemokines in regulating host immunity in children with Plasmodium falciparum malaria has not previously been reported, circulating levels of beta-chemokines (MIP-1alpha, MIP-1beta, and RANTES) and their respective transcriptional profiles in ex vivo peripheral blood mononuclear cells (PBMCs) were investigated. Peripheral blood MIP-1alpha and MIP-1beta levels were significantly elevated in mild and severe malaria, while RANTES levels decreased with increasing disease severity. Beta-chemokine gene expression profiles in blood mononuclear cells closely matched those of circulating beta-chemokines, illustrating that PBMCs are a primary source for the observed pattern of beta-chemokine production during acute malaria. Statistical modeling revealed that none of the chemokines was significantly associated with either parasitemia or anemia. Additional investigations in healthy children with a known history of malaria showed that children with prior severe malaria had significantly lower baseline RANTES production than children with a history of mild malaria, suggesting inherent differences in the ability to produce RANTES in these two groups. Baseline MIP-1alpha and MIP-1beta did not significantly differ between children with prior severe malaria and those with mild malaria. Additional in vitro experiments in PBMCs from healthy, malaria-naïve donors revealed that P. falciparum-derived hemozoin (Hz; malarial pigment) and synthetic Hz (beta-hematin) promote a similar pattern of beta-chemokine gene expression. Taken together, the results presented here demonstrate that children with severe malaria have a distinct profile of beta-chemokines characterized by increased circulating levels of MIP-1alpha and MIP-1beta and decreased RANTES. Altered patterns of circulating beta-chemokines result, at least in part, from Hz-induced changes in beta-chemokine gene expression in blood mononuclear cells.

Full Text

Duke Authors

Cited Authors

  • Ochiel, DO; Awandare, GA; Keller, CC; Hittner, JB; Kremsner, PG; Weinberg, JB; Perkins, DJ

Published Date

  • July 2005

Published In

Volume / Issue

  • 73 / 7

Start / End Page

  • 4190 - 4197

PubMed ID

  • 15972509

Pubmed Central ID

  • 15972509

International Standard Serial Number (ISSN)

  • 0019-9567

Digital Object Identifier (DOI)

  • 10.1128/IAI.73.7.4190-4197.2005

Language

  • eng

Conference Location

  • United States