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Trypanosoma brucei gambiense excreted/secreted factors impair lipopolysaccharide‐induced maturation and activation of human monocyte‐derived dendritic cells
Author(s) -
Dauchy FrédéricAntoine,
ContinBordes Cécile,
NzoumbouBoko Romaric,
Bonhivers Mélanie,
Landrein Nicolas,
Robinson Derrick R.,
Rambert Jérôme,
Courtois Pierrette,
Daulouède Sylvie,
Vincendeau Philippe
Publication year - 2019
Publication title -
parasite immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 75
eISSN - 1365-3024
pISSN - 0141-9838
DOI - 10.1111/pim.12632
Subject(s) - biology , immune system , lipopolysaccharide , immunology , secretion , innate immune system , microbiology and biotechnology , trypanosoma brucei , monocyte , cytokine , endocrinology , biochemistry , gene
Trypanosoma brucei gambiense , an extracellular eukaryotic flagellate parasite, is the main etiological agent of human African trypanosomiasis ( HAT ) or sleeping sickness. Dendritic cells ( DC s) 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 DC s (Mo‐ DC s). Mo‐ DC s 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 CD 83, as well as the secretion of IL ‐12, TNF ‐alpha and IL ‐10, in LPS ‐stimulated Mo‐ DC s. During mixed‐leucocyte reactions, LPS ‐ plus ESF ‐exposed DC s induced a non‐significant decrease in the IFN ‐gamma/ IL ‐10 ratio of CD 4 + 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 DC s. The identification of the factor(s) in the T gambiense ESF and of the DC s signalling pathway(s) involved may be important in the development of new therapeutic targets.