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Monocyte polarization in children with falciparum malaria: relationship to nitric oxide insufficiency and disease severity

Year: 2016
Type: article
Study design: Observational Study
Abstract: We earlier established that nitric oxide (NO) is protective against severe malaria and that arginine and NO levels are reduced in malaria patients. We now show that an M2-like blood monocyte phenotype is significantly associated with hypoargininemia, NO insufficiency, and disease severity in Tanzanian children with falciparum malaria. Compared to control children (n = 106), children with moderately severe (n = 77) and severe falciparum malaria (n = 129) had significantly higher mononuclear cell arginase 1 mRNA, protein, and enzyme activity; lower NOS2 mRNA; lower plasma arginine; and higher plasma IL-10, IL-13, and IL-4. In addition, monocyte CD206 and CD163 and plasma soluble CD163 were elevated. Multivariate logistic regression analysis revealed a significant correlation of risk of severe malaria with both plasma IL-10 and soluble CD163 levels. Monocyte M2 skewing likely contributes to NO bioinsufficiency in falciparum malaria in children. Treatments that reverse the M2 polarization may have potential as adjunctive treatment for malaria.
DOI: 10.1038/srep29151
Authors: J. Brice Weinberg, Alicia D. Volkheimer, Matthew P. Rubach, Salvatore M. Florence, Jackson P. Mukemba, Ayam R. Kalingonji, Charles Langelier, Youwei Chen, Margaret Bush, Tsin W. Yeo, Donald L. Granger, Nicholas M. Anstey, Esther D. Mwaikambo
Institutions: Duke University, Duke Medical Center, Hubert Kairuki Memorial University, University of California, San Francisco, Charles Darwin University, Menzies School of Health Research, University of Utah
Language: English
Field: Medicine
Open Access status: gold
Estimated APC paid: $2,690
Funders: U.S. Department of Veterans Affairs, American Society of Tropical Medicine and Hygiene, National Institutes of Health, Medical Research Council, National Health and Medical Research Council, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases
Awards: Nitric Oxide and Microvascular Dysfunction in Severe Malaria, Hyperphenylalaninemia in cerebral malaria, Arginine, Nitric Oxide, and Severe Malaria, UCSF Career Development Program in Omics of Lung Diseases, Tropical Disease - immunity, pathogenesis and vaccine development: global translation, Nitric Oxide and Severe Malaria, Nitric Oxide and Malaria, Hyperphenylalaninemia in cerebral malaria
OpenAlex ID: W2472611930
FWCI: 6.612
Cites: 65
Cited by: 47
Related to: 10