Insights into deregulated TNF and IL-10 production in malaria: implications for understanding severe malarial anaemia.

Philippe Boeuf (1) , Séverine Loizon (1, 2) , Gordon Awandare (3) , John Tetteh (4) , Michael Addae (5) , George Adjei (6) , Bamenla Goka (6) , Jørgen Al Kurtzhals (7, 8, 9, 10) , Odile Puijalon (1) , Lars Hviid (6) , Bartholomew Akanmori (4) , Charlotte Behr (1, 2)

1 Immunologie moléculaire des parasites
2 CIRID - Composantes innées de la réponse immunitaire et différenciation
3 Immunology Department
4 Immunology Department
5 Department of Hematology
6 Department of Child Health
7 Centre for Medical Parasitology [Copenhagen]
8 Department of Clinical Microbiology [Rigshospitalet]
9 Department of Infectious Diseases
10 Department of Immunology and Microbiology [Copenhagen]

UNLABELLED: 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.

Domains: Life Sciences [q-bio]; Human health and pathology; Infectious diseases

Philippe Boeuf, Séverine Loizon, Gordon Awandare, John Tetteh, Michael Addae, et al.. Insights into deregulated TNF and IL-10 production in malaria: implications for understanding severe malarial anaemia.. Malaria Journal, 2012, 11 (1), pp.253. ⟨10.1186/1475-2875-11-253⟩. ⟨pasteur-00741163⟩