title: Monocyte activation and cytokine production in Malawian children presenting with P. falciparum malaria.
abstract: Malaria in malaria-naïve adults is associated with an inflammatory response characterized by expression of specific activation markers on innate immune cells. Here, we investigate activation and adhesion marker expression, and cytokine production in monocytes from children presenting with cerebral malaria (CM, n = 36), severe malarial anaemia (SMA, n = 42) or uncomplicated malaria (UM, n = 66), and healthy aparasitemic children (n = 52) in Blantyre, Malawi. In all malaria groups, but particularly in the two severe malaria groups, monocyte expression of CD11b, CD11c, CD18, HLA-DR and CD86, and percentages of TNF-α- and IL-6-producing monocytes were lower than in healthy controls, while expression of CD11a, TLR2 and TLR4 was lower in children with severe malaria compared with controls. These levels mostly normalized during convalescence, but percentages of cytokine-producing monocytes remained suppressed in children with SMA. In all malaria groups, especially the SMA group, a greater proportion of monocytes were loaded with haemozoin than among controls. In a P. falciparum hyperendemic area, monocytes in children with acute symptomatic malaria have reduced expression of adhesion molecules and activation markers and reduced inflammatory cytokine production. This immune suppression could be due to accumulation of haemozoin and/or previous exposure to P. falciparum.
authors.affiliation: Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi.|Department of Biomedical Sciences, College of Medicine, University of Malawi, Blantyre, Malawi.|Liverpool School of Tropical Medicine, Pembroke Place, University of Liverpool, Liverpool, UK.
authors.forename: W L
authors.initials: WL
authors.lastname: Mandala
authors.affiliation: Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi.|Liverpool School of Tropical Medicine, Pembroke Place, University of Liverpool, Liverpool, UK.
authors.forename: C L
authors.initials: CL
authors.lastname: Msefula
authors.affiliation: Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi.|Liverpool School of Tropical Medicine, Pembroke Place, University of Liverpool, Liverpool, UK.
authors.forename: E N
authors.initials: EN
authors.lastname: Gondwe
authors.affiliation: Medical Research Council Centre for Immune Regulation and Clinical Immunology Service, Institute of Biomedical Research, School of Immunity and Infection, College of Medicine and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: M T
authors.initials: MT
authors.lastname: Drayson
authors.affiliation: Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi.|Liverpool School of Tropical Medicine, Pembroke Place, University of Liverpool, Liverpool, UK.|Department of Medicine, College of Medicine, University of Malawi, Blantyre, Malawi.
authors.forename: M E
authors.initials: ME
authors.lastname: Molyneux
authors.affiliation: Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi.|Medical Research Council Centre for Immune Regulation and Clinical Immunology Service, Institute of Biomedical Research, School of Immunity and Infection, College of Medicine and Dental Sciences, University of Birmingham, Birmingham, UK.|The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: C A
authors.initials: CA
authors.lastname: MacLennan
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D002648:Child; D016207:Cytokines / Q000032:analysis; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007223:Infant; D016023:Integrins / Q000032:analysis; D008288:Malaria / Q000276:immunology*; D016779:Malaria, Cerebral / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology*; D008297:Male; D009000:Monocytes / Q000737:chemistry / Q000276:immunology*; D051193:Toll-Like Receptors / Q000032:analysis
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D006684:HLA-DR Antigens; D016023:Integrins; D051193:Toll-Like Receptors
keywords: integrins; monocytes; toll-like receptors and cytokines