Trypanosoma brucei gambiense excreted/secreted factors impair lipopolysaccharide-induced maturation and activation of human monocyte-derived dendritic cells.
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.
['Dauchy|Frédéric-Antoine|FA|0000-0002-7727-2851', 'Contin-Bordes|Cécile|C|', 'Nzoumbou-Boko|Romaric|R|', 'Bonhivers|Mélanie|M|', 'Landrein|Nicolas|N|', 'Robinson|Derrick R|DR|', 'Rambert|Jérôme|J|', 'Courtois|Pierrette|P|', 'Daulouède|Sylvie|S|', 'Vincendeau|Philippe|P|']
D000818:Animals D003713:Dendritic Cells D005260:Female D006684:HLA-DR Antigens D006790:Host-Parasite Interactions D006801:Humans D016753:Interleukin-10 D018664:Interleukin-12 D008070:Lipopolysaccharides D051379:Mice D009000:Monocytes D015800:Protozoan Proteins D015398:Signal Transduction D013601:T-Lymphocytes D014347:Trypanosoma brucei gambiense D014353:Trypanosomiasis, African D014409:Tumor Necrosis Factor-alpha
dendritic cell < cell inflammation < disease trypanosomiasis < disease