1. Insights into deregulated TNF and IL-10 production in malaria: implications for understanding severe malarial anaemia
- Author
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Gordon A. Awandare, Michael M Addae, Séverine Loizon, Bamenla Q. Goka, Lars Hviid, Philippe Boeuf, Charlotte Behr, Odile Puijalon, John Tetteh, Jørgen A. L. Kurtzhals, George O. Adjei, Bartholomew D. Akanmori, Immunologie moléculaire des parasites, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Immunology Department, University of Ghana, Noguchi Memorial Institute for Medical Research [Accra, Ghana] (NMIMR), University of Ghana-University of Ghana, Department of Hematology, Department of Child Health, Centre for Medical Parasitology [Copenhagen], Department of Immunology and Microbiology [Copenhagen], Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Department of Clinical Microbiology [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Department of Infectious Diseases, European programs INCO-DC (grant n° IC18-CT-980370), the WHO/TDR/MIM project 980037, the Enhancement of Research Capacity in Developing Countries (ENRECA) program of the Danish International Development Assistance (Danida), grant n° 14.Dan.8.L.306 and the PAL + program from the French Ministry of Research and Technology Caisse Nationale d'Assurances Maladies, France, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Faculty of Health and Medical Sciences, and University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)
- Subjects
Antigens, Differentiation, T-Lymphocyte ,Male ,Lipopolysaccharide ,T-Lymphocytes ,Lymphocyte Activation ,Monocytes ,chemistry.chemical_compound ,0302 clinical medicine ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Child ,Cerebral malaria ,0303 health sciences ,SMA ,Flow Cytometry ,Severe malarial anaemia ,Monocyte de-activation, TNF ,3. Good health ,Interleukin-10 ,Interleukin 10 ,Infectious Diseases ,medicine.anatomical_structure ,Child, Preschool ,IL-10 ,Erythropoiesis ,Cytokines ,Tumor necrosis factor alpha ,Female ,lcsh:Arctic medicine. Tropical medicine ,lcsh:RC955-962 ,T cell ,030231 tropical medicine ,T cells ,Anaemia ,Biology ,lcsh:Infectious and parasitic diseases ,03 medical and health sciences ,Antigen ,Antigens, CD ,medicine ,Humans ,Lectins, C-Type ,lcsh:RC109-216 ,CD69 ,030304 developmental biology ,Tumor Necrosis Factor-alpha ,Monocyte ,Research ,HLA-DR ,Infant ,HLA-DR Antigens ,Malaria ,chemistry ,Immunology ,Parasitology - Abstract
Background Severe malarial anaemia (SMA) is a major life-threatening complication of paediatric malaria. Protracted production of pro-inflammatory cytokines promoting erythrophagocytosis and depressing erythropoiesis is thought to play an important role in SMA, which is characterized by a high TNF/IL-10 ratio. Whether this TNF/IL-10 imbalance results from an intrinsic incapacity of SMA patients to produce IL-10 or from an IL-10 unresponsiveness to infection is unknown. Monocytes and T cells are recognized as the main sources of TNF and IL-10 in vivo, but little is known about the activation status of those cells in SMA patients. Methods The IL-10 and TNF production capacity and the activation phenotype of monocytes and T cells were compared in samples collected from 332 Ghanaian children with non-overlapping SMA (n = 108), cerebral malaria (CM) (n = 144) or uncomplicated malaria (UM) (n = 80) syndromes. Activation status of monocytes and T cells was ascertained by measuring HLA-DR+ and/or CD69+ surface expression by flow cytometry. The TNF and IL-10 production was assessed in a whole-blood assay after or not stimulation with lipopolysaccharide (LPS) or phytohaemaglutinin (PHA) used as surrogate of unspecific monocyte and T cell stimulant. The number of circulating pigmented monocytes was also determined. Results Monocytes and T cells from SMA and CM patients showed similar activation profiles with a comparable decreased HLA-DR expression on monocytes and increased frequency of CD69+ and HLA-DR+ T cells. In contrast, the acute-phase IL-10 production was markedly decreased in SMA compared to CM (P = .003) and UM (P = .004). Although in SMA the IL-10 response to LPS-stimulation was larger in amplitude than in CM (P = .0082), the absolute levels of IL-10 reached were lower (P = .013). Both the amplitude and levels of TNF produced in response to LPS-stimulation were larger in SMA than CM (P = .019). In response to PHA-stimulation, absolute levels of IL-10 produced in SMA were lower than in CM (P = .005) contrasting with TNF levels, which were higher (P = .001). Conclusions These data reveal that SMA patients have the potential to mount efficient IL-10 responses and that the TNF/IL-10 imbalance may reflect a specific monocyte and T cell programming/polarization pattern in response to infection.
- Published
- 2012