Naturally acquired hemozoin by monocytes promotes suppression of RANTES in children with malarial anemia through an IL-10-dependent mechanism

Regulated upon activation, normal T-cell expressed, and secreted (RANTES, CCL-5) is an important immunoregulatory mediator that is suppressed in children with malarial anemia (MA). Although pro-inflammatory (e.g., TNF-α, IL-1β and IFN-γ) and anti-inflammatory (e.g., IL-4, IL-10 and IL-13) cytokines...

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Published in:	Microbes and infection Vol. 11; no. 8; pp. 811 - 819
Main Authors:	Were, Tom, Davenport, Gregory C., Yamo, Emmanuel O., Hittner, James B., Awandare, Gordon A., Otieno, Michael F., Ouma, Collins, Orago, Alloys S.S., Vulule, John M., Ong'echa, John M., Perkins, Douglas J.
Format:	Journal Article
Language:	English
Published:	Kidlington Elsevier SAS 01-07-2009 Elsevier
Subjects:	Anemia, Hemolytic - immunology Anemia, Hemolytic - metabolism Biological and medical sciences Chemokine CCL5 - biosynthesis Chemokine CCL5 - blood Child, Preschool Cytokines - metabolism Female Fundamental and applied biological sciences. Psychology Hemeproteins - metabolism Hemozoin Human protozoal diseases Humans IL-10 Infant Infectious diseases Interleukin-10 - metabolism Malaria Malaria, Falciparum - immunology Malaria, Falciparum - metabolism Male Medical sciences Microbiology Monocytes Monocytes - immunology Monocytes - metabolism Neutrophils - immunology Parasitic diseases Phagocytosis Protozoal diseases RANTES Monocytes Malaria RANTES Hemozoin IL-10 Human Protozoal disease Monocyte Anemia Suppression Cytokine Hemopathy Parasitosis Mechanism Infection Chemokine Interleukin 10 Child
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Summary:	Regulated upon activation, normal T-cell expressed, and secreted (RANTES, CCL-5) is an important immunoregulatory mediator that is suppressed in children with malarial anemia (MA). Although pro-inflammatory (e.g., TNF-α, IL-1β and IFN-γ) and anti-inflammatory (e.g., IL-4, IL-10 and IL-13) cytokines regulate RANTES production, their effect on RANTES in children with MA has not been determined. Since intraleukocytic malarial pigment, hemozoin (Hz), causes dysregulation in chemokine and cytokine production, the impact of naturally acquired Hz ( pfHz) on RANTES and RANTES-regulatory cytokines (TNF-α, IFN-γ, IL-1β, IL-4, IL-10, and IL-13) was examined. Circulating RANTES levels progressively declined with increasing levels of pigment-containing monocytes (PCM) ( P = 0.035). Additional experiments in cultured peripheral blood mononuclear cells (PBMC) showed that monocytic acquisition of pfHz ( in vivo) was associated with suppression of RANTES under baseline ( P = 0.001) and stimulated conditions ( P = 0.072). Although high PCM levels were associated with decreased circulating IFN-γ ( P = 0.003) and IL-10 ( P = 0.010), multivariate modeling revealed that only PCM ( P = 0.048, β = −0.171) and IL-10 ( P < 0.0001, β = −0.476) were independently associated with RANTES production. Subsequent in vitro experiments revealed that blockade of endogenous IL-10 significantly increased RANTES production ( P = 0.028) in PBMC from children with naturally acquired Hz. Results here demonstrate that monocytic acquisition of Hz suppresses RANTES production in children with MA through an IL-10-dependent mechanism.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1286-4579 1769-714X
DOI:	10.1016/j.micinf.2009.04.021