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

Parasite Immunol. 2019 Aug;41(8):e12632. doi: 10.1111/pim.12632. Epub 2019 Jun 27.


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.

Keywords: dendritic cell < cell; inflammation < disease; trypanosomiasis < disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dendritic Cells / immunology*
  • Dendritic Cells / parasitology
  • Female
  • HLA-DR Antigens / genetics
  • HLA-DR Antigens / immunology
  • Host-Parasite Interactions
  • Humans
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology
  • Interleukin-12 / genetics
  • Interleukin-12 / immunology
  • Lipopolysaccharides / immunology
  • Mice
  • Monocytes / immunology*
  • Monocytes / parasitology
  • Protozoan Proteins / genetics
  • Protozoan Proteins / immunology*
  • Signal Transduction
  • T-Lymphocytes / immunology
  • T-Lymphocytes / parasitology
  • Trypanosoma brucei gambiense / genetics
  • Trypanosoma brucei gambiense / immunology*
  • Trypanosomiasis, African / genetics
  • Trypanosomiasis, African / immunology*
  • Trypanosomiasis, African / parasitology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology


  • HLA-DR Antigens
  • Lipopolysaccharides
  • Protozoan Proteins
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-12