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Monocyte dysregulation and systemic inflammation during pediatric falciparum malaria
Katherine R. Dobbs, … , James W. Kazura, Arlene E. Dent
Katherine R. Dobbs, … , James W. Kazura, Arlene E. Dent
Published September 21, 2017
Citation Information: JCI Insight. 2017;2(18):e95352. doi:10.1172/jci.insight.95352.
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Categories: Clinical Medicine Immunology Infectious disease

Monocyte dysregulation and systemic inflammation during pediatric falciparum malaria

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Abstract

BACKGROUND. Inflammation and monocytes are thought to be important to human malaria pathogenesis. However, the relationship of inflammation and various monocyte functions to acute malaria, recovery from acute malaria, and asymptomatic parasitemia in endemic populations is poorly understood. METHODS. We evaluated plasma cytokine levels, monocyte subsets, monocyte functional responses, and monocyte inflammatory transcriptional profiles of 1- to 10-year-old Kenyan children at the time of presentation with acute uncomplicated malaria and at recovery 6 weeks later; these results were compared with analogous data from asymptomatic children and adults in the same community. RESULTS. Acute malaria was marked by elevated levels of proinflammatory and regulatory cytokines and expansion of the inflammatory “intermediate” monocyte subset that returned to levels of healthy asymptomatic children 6 weeks later. Monocytes displayed activated phenotypes during acute malaria, with changes in surface expression of markers important to innate and adaptive immunity. Functionally, acute malaria monocytes and monocytes from asymptomatic infected children had impaired phagocytosis of P. falciparum–infected erythrocytes relative to asymptomatic children with no blood-stage infection. Monocytes from both acute malaria and recovery time points displayed strong and equivalent cytokine responsiveness to innate immune agonists that were independent of infection status. Monocyte transcriptional profiles revealed regulated and balanced proinflammatory and antiinflammatory and altered phagocytosis gene expression patterns distinct from malaria-naive monocytes. CONCLUSION. These observations provide insights into monocyte functions and the innate immune response during uncomplicated malaria and suggest that asymptomatic parasitemia in children is not clinically benign. FUNDING. Support for this work was provided by NIH/National Institute of Allergy and Infectious Diseases (R01AI095192-05), the Burroughs Wellcome Fund/American Society of Tropical Medicine and Hygiene, and the Rainbow Babies & Children’s Foundation.

Authors

Katherine R. Dobbs, Paula Embury, John Vulule, Peter S. Odada, Bruce A. Rosa, Makedonka Mitreva, James W. Kazura, Arlene E. Dent

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Figure 1

Acute uncomplicated malaria is associated with a robust proinflammatory cytokine response and systemic inflammation.

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Acute uncomplicated malaria is associated with a robust proinflammatory ...
Plasma cytokine and acute-phase reactant levels were compared in samples from cases of acute uncomplicated malaria and 6-week recovery samples (n = 60 pairs) and samples from heathy child controls (n = 40). Bars represent medians with interquartile ranges. Wilcoxon matched-pairs rank test was used to compare acute malaria samples to 6-week recovery samples. Kruskal-Wallis test was used to compare healthy child samples to acute malaria and 6-week recovery samples. ****P < 0.0001. IP-10, IFN-γ–induced protein 10.
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