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

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

Author information

1
Laboratoire de Parasitologie, UMR IRD CIRAD INTERTRYP 177, University of Bordeaux, Bordeaux, France.
2
UMR INTERTRYP 177, IRD-CIRAD-University of Bordeaux, Montpellier, France.
3
Department of Infectious and Tropical Diseases, Hôpital Pellegrin, CHU de Bordeaux, Bordeaux, France.
4
Laboratoire d'Immunologie et d'Immunogénétique, CHU de Bordeaux, Bordeaux, France.
5
UMR 5164 CIRID, University of Bordeaux, Bordeaux, France.
6
Microbiologie Fondamentale et Pathogénicité, UMR 5234, University of Bordeaux, Bordeaux, France.
7
Microbiologie Fondamentale et Pathogénicité, UMR 5234, CNRS, Bordeaux, France.
8
Aquiderm, INSERM U 1035, University of Bordeaux, Bordeaux, France.
9
Laboratoire de Parasitologie, CHU de Bordeaux, Bordeaux, France.

Abstract

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

PMID:
31099071
DOI:
10.1111/pim.12632

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