DAUCHY, Frederic-Antoine; CONTIN-BORDES, C.; NZOUMBOU-BOKO, R.; BONHIVERS, M.; LANDREIN, N.; ROBINSON, D. R.; RAMBERT, J.; COURTOIS, P.; DAULOUEDE, S.; VINCENDEAU, P.

doi:10.1111/pim.12632

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DAUCHY, Frederic-Antoine
Bordeaux population health [BPH]

CONTIN-BORDES, C.

NZOUMBOU-BOKO, R.

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Parasite Immunol. 2019-08, vol. 41, n° 8, p. e12632

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Trypanosoma brucei gambiense, an extracellular eukaryotic flagellate parasite, is the main etiological agent of human African trypanosomiasis (HAT) or sleeping sickness. Dendritic cells (DCs) play a pivotal role at the interface between innate and adaptive immune response and are implicated during HAT. In this study, we investigated the effects of T gambiense and its excreted/secreted factors (ESF) on the phenotype of human monocyte-derived DCs (Mo-DCs). Mo-DCs were cultured with trypanosomes, lipopolysaccharide (LPS), ESF derived from T gambiense bloodstream strain Biyamina (MHOM/SD/82), or both ESF and LPS. Importantly, ESF reduced the expression of the maturation markers HLA-DR and CD83, as well as the secretion of IL-12, TNF-alpha and IL-10, in LPS-stimulated Mo-DCs. During mixed-leucocyte reactions, LPS- plus ESF-exposed DCs induced a non-significant decrease in the IFN-gamma/IL-10 ratio of CD4 + T-cell cytokines. Based on the results presented here, we raise the hypothesis that T gambiense has developed an immune escape strategy through the secretion of paracrine mediators in order to limit maturation and activation of human DCs. The identification of the factor(s) in the T gambiense ESF and of the DCs signalling pathway(s) involved may be important in the development of new therapeutic targets.< Réduire

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Trypanosoma brucei gambiense excreted/secreted factors impair lipopolysaccharide-induced maturation and activation of human monocyte-derived dendritic cells

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