Differential Regulation of β-Chemokines in Children with Plasmodium falciparum Malaria
| Autor: | James B. Hittner, J. Brice Weinberg, Daniel O. Ochiel, Peter G. Kremsner, Christopher C. Keller, Gordon A. Awandare, Douglas J. Perkins |
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| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Hemeproteins
Male Chemokine Immunology Parasitemia Biology Microbiology Peripheral blood mononuclear cell Hemoglobins Immune system parasitic diseases medicine Humans Malaria Falciparum Chemokine CCL4 Child Macrophage inflammatory protein Chemokine CCL5 Chemokine CCL3 Hemozoin Gene Expression Profiling Plasmodium falciparum Macrophage Inflammatory Proteins medicine.disease biology.organism_classification Infectious Diseases Child Preschool biology.protein Parasitology Female Fungal and Parasitic Infections Malaria |
| Popis: | 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 β-chemokines (MIP-1α, MIP-1β, and RANTES) and their respective transcriptional profiles in ex vivo peripheral blood mononuclear cells (PBMCs) were investigated. Peripheral blood MIP-1α and MIP-1β levels were significantly elevated in mild and severe malaria, while RANTES levels decreased with increasing disease severity. β-Chemokine gene expression profiles in blood mononuclear cells closely matched those of circulating β-chemokines, illustrating that PBMCs are a primary source for the observed pattern of β-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-1α and MIP-1β 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 (β-hematin) promote a similar pattern of β-chemokine gene expression. Taken together, the results presented here demonstrate that children with severe malaria have a distinct profile of β-chemokines characterized by increased circulating levels of MIP-1α and MIP-1β and decreased RANTES. Altered patterns of circulating β-chemokines result, at least in part, from Hz-induced changes in β-chemokine gene expression in blood mononuclear cells. |
| Databáze: | OpenAIRE |
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