title: Monocyte polarization in children with falciparum malaria: relationship to nitric oxide insufficiency and disease severity.
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.
authors.affiliation: Duke University and V.A. Medical Centers, Durham, North Carolina, USA.
authors.forename: J Brice
authors.initials: JB
authors.lastname: Weinberg
authors.affiliation: Duke University and V.A. Medical Centers, Durham, North Carolina, USA.
authors.forename: Alicia D
authors.initials: AD
authors.lastname: Volkheimer
authors.affiliation: Duke University and V.A. Medical Centers, Durham, North Carolina, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Rubach
authors.affiliation: Hubert Kairuki Memorial University, Dar es Salaam, Tanzania.
authors.forename: Salvatore M
authors.initials: SM
authors.lastname: Florence
authors.affiliation: Hubert Kairuki Memorial University, Dar es Salaam, Tanzania.
authors.forename: Jackson P
authors.initials: JP
authors.lastname: Mukemba
authors.affiliation: Hubert Kairuki Memorial University, Dar es Salaam, Tanzania.
authors.forename: Ayam R
authors.initials: AR
authors.lastname: Kalingonji
authors.affiliation: University of California at San Francisco, CA, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Langelier
authors.affiliation: Duke University and V.A. Medical Centers, Durham, North Carolina, USA.
authors.forename: Youwei
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Duke University and V.A. Medical Centers, Durham, North Carolina, USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Bush
authors.affiliation: Menzies School of Health Research and Charles Darwin University, Darwin, Australia.
authors.forename: Tsin W
authors.initials: TW
authors.lastname: Yeo
authors.affiliation: University of Utah and V.A. Medical Centers, Salt Lake City, Utah, USA.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Granger
authors.affiliation: Menzies School of Health Research and Charles Darwin University, Darwin, Australia.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Anstey
authors.affiliation: Hubert Kairuki Memorial University, Dar es Salaam, Tanzania.
authors.forename: Esther D
authors.initials: ED
authors.lastname: Mwaikambo
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D001119:Arginase / Q000097:blood; D001120:Arginine / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016764:Cell Polarity; D018925:Chemokines / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood / Q000473:pathology*; D008297:Male; D008954:Models, Biological; D009000:Monocytes / Q000473:pathology*; D009569:Nitric Oxide / Q000378:metabolism*; D010586:Phagocytes / Q000378:metabolism; D012720:Severity of Illness Index
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D018925:Chemokines; D009569:Nitric Oxide; D001120:Arginine; C574619:ARG1 protein, human; D001119:Arginase