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

J Brice Weinberg; Alicia Volkheimer; Matthew Rubach; Salvatore Florence; Jackson Mukemba; AR Kalingonji; C Langelier; Y Chen; M Bush; Tsin Yeo; Donald Granger; Nicholas Anstey; Esther Mwaikambo

doi:10.1038/srep29151

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

J Brice Weinberg, Alicia Volkheimer, Matthew Rubach, Salvatore Florence, Jackson Mukemba, AR Kalingonji, C Langelier, Y Chen, M Bush, Tsin Yeo, Donald Granger, Nicholas Anstey, Esther Mwaikambo

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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.

Original language	English
Article number	29151
Pages (from-to)	1-13
Number of pages	13
Journal	Scientific Reports
Volume	6
DOIs	https://doi.org/10.1038/srep29151
Publication status	Published - 2016

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Weinberg, J. B., Volkheimer, A., Rubach, M., Florence, S., Mukemba, J., Kalingonji, AR., Langelier, C., Chen, Y., Bush, M., Yeo, T., Granger, D., Anstey, N., & Mwaikambo, E. (2016). Monocyte polarization in children with falciparum malaria: Relationship to nitric oxide insufficiency and disease severity. Scientific Reports, 6, 1-13. [29151]. https://doi.org/10.1038/srep29151

Weinberg, J Brice ; Volkheimer, Alicia ; Rubach, Matthew ; Florence, Salvatore ; Mukemba, Jackson ; Kalingonji, AR ; Langelier, C ; Chen, Y ; Bush, M ; Yeo, Tsin ; Granger, Donald ; Anstey, Nicholas ; Mwaikambo, Esther. / Monocyte polarization in children with falciparum malaria : Relationship to nitric oxide insufficiency and disease severity. In: Scientific Reports. 2016 ; Vol. 6. pp. 1-13.

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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.",

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Monocyte polarization in children with falciparum malaria : Relationship to nitric oxide insufficiency and disease severity. / Weinberg, J Brice; Volkheimer, Alicia; Rubach, Matthew; Florence, Salvatore; Mukemba, Jackson; Kalingonji, AR; Langelier, C; Chen, Y; Bush, M; Yeo, Tsin; Granger, Donald; Anstey, Nicholas; Mwaikambo, Esther.

In: Scientific Reports, Vol. 6, 29151, 2016, p. 1-13.

Research output: Contribution to journal › Article

TY - JOUR

T1 - Monocyte polarization in children with falciparum malaria

T2 - Relationship to nitric oxide insufficiency and disease severity

AU - Weinberg, J Brice

AU - Volkheimer, Alicia

AU - Rubach, Matthew

AU - Florence, Salvatore

AU - Mukemba, Jackson

AU - Kalingonji, AR

AU - Langelier, C

AU - Chen, Y

AU - Bush, M

AU - Yeo, Tsin

AU - Granger, Donald

AU - Anstey, Nicholas

AU - Mwaikambo, Esther

PY - 2016

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N2 - 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.

AB - 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.

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