PMID- 31099071 OWN - NLM STAT- MEDLINE DCOM- 20200210 LR - 20200210 IS - 1365-3024 (Electronic) IS - 0141-9838 (Linking) VI - 41 IP - 8 DP - 2019 Aug TI - Trypanosoma brucei gambiense excreted/secreted factors impair lipopolysaccharide-induced maturation and activation of human monocyte-derived dendritic cells. PG - e12632 LID - 10.1111/pim.12632 [doi] AB - 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. CI - (c) 2019 John Wiley & Sons Ltd. FAU - Dauchy, Frederic-Antoine AU - Dauchy FA AUID- ORCID: 0000-0002-7727-2851 AD - Laboratoire de Parasitologie, UMR IRD CIRAD INTERTRYP 177, University of Bordeaux, Bordeaux, France. AD - UMR INTERTRYP 177, IRD-CIRAD-University of Bordeaux, Montpellier, France. AD - Department of Infectious and Tropical Diseases, Hopital Pellegrin, CHU de Bordeaux, Bordeaux, France. FAU - Contin-Bordes, Cecile AU - Contin-Bordes C AD - Laboratoire d'Immunologie et d'Immunogenetique, CHU de Bordeaux, Bordeaux, France. AD - UMR 5164 CIRID, University of Bordeaux, Bordeaux, France. FAU - Nzoumbou-Boko, Romaric AU - Nzoumbou-Boko R AD - Laboratoire de Parasitologie, UMR IRD CIRAD INTERTRYP 177, University of Bordeaux, Bordeaux, France. AD - UMR INTERTRYP 177, IRD-CIRAD-University of Bordeaux, Montpellier, France. FAU - Bonhivers, Melanie AU - Bonhivers M AD - Microbiologie Fondamentale et Pathogenicite, UMR 5234, University of Bordeaux, Bordeaux, France. AD - Microbiologie Fondamentale et Pathogenicite, UMR 5234, CNRS, Bordeaux, France. FAU - Landrein, Nicolas AU - Landrein N AD - Microbiologie Fondamentale et Pathogenicite, UMR 5234, University of Bordeaux, Bordeaux, France. AD - Microbiologie Fondamentale et Pathogenicite, UMR 5234, CNRS, Bordeaux, France. FAU - Robinson, Derrick R AU - Robinson DR AD - Microbiologie Fondamentale et Pathogenicite, UMR 5234, University of Bordeaux, Bordeaux, France. AD - Microbiologie Fondamentale et Pathogenicite, UMR 5234, CNRS, Bordeaux, France. FAU - Rambert, Jerome AU - Rambert J AD - Aquiderm, INSERM U 1035, University of Bordeaux, Bordeaux, France. FAU - Courtois, Pierrette AU - Courtois P AD - Laboratoire de Parasitologie, UMR IRD CIRAD INTERTRYP 177, University of Bordeaux, Bordeaux, France. AD - UMR INTERTRYP 177, IRD-CIRAD-University of Bordeaux, Montpellier, France. FAU - Daulouede, Sylvie AU - Daulouede S AD - Laboratoire de Parasitologie, UMR IRD CIRAD INTERTRYP 177, University of Bordeaux, Bordeaux, France. AD - UMR INTERTRYP 177, IRD-CIRAD-University of Bordeaux, Montpellier, France. FAU - Vincendeau, Philippe AU - Vincendeau P AD - Laboratoire de Parasitologie, UMR IRD CIRAD INTERTRYP 177, University of Bordeaux, Bordeaux, France. AD - UMR INTERTRYP 177, IRD-CIRAD-University of Bordeaux, Montpellier, France. AD - Laboratoire de Parasitologie, CHU de Bordeaux, Bordeaux, France. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190627 PL - England TA - Parasite Immunol JT - Parasite immunology JID - 7910948 RN - 0 (HLA-DR Antigens) RN - 0 (Lipopolysaccharides) RN - 0 (Protozoan Proteins) RN - 0 (Tumor Necrosis Factor-alpha) RN - 130068-27-8 (Interleukin-10) RN - 187348-17-0 (Interleukin-12) SB - IM MH - Animals MH - Dendritic Cells/*immunology/parasitology MH - Female MH - HLA-DR Antigens/genetics/immunology MH - Host-Parasite Interactions MH - Humans MH - Interleukin-10/genetics/immunology MH - Interleukin-12/genetics/immunology MH - Lipopolysaccharides/immunology MH - Mice MH - Monocytes/*immunology/parasitology MH - Protozoan Proteins/genetics/*immunology MH - Signal Transduction MH - T-Lymphocytes/immunology/parasitology MH - Trypanosoma brucei gambiense/genetics/*immunology MH - Trypanosomiasis, African/genetics/*immunology/parasitology MH - Tumor Necrosis Factor-alpha/genetics/immunology OTO - NOTNLM OT - dendritic cell < cell OT - inflammation < disease OT - trypanosomiasis < disease EDAT- 2019/05/18 06:00 MHDA- 2020/02/11 06:00 CRDT- 2019/05/18 06:00 PHST- 2019/03/11 00:00 [received] PHST- 2019/05/13 00:00 [revised] PHST- 2019/05/14 00:00 [accepted] PHST- 2019/05/18 06:00 [pubmed] PHST- 2020/02/11 06:00 [medline] PHST- 2019/05/18 06:00 [entrez] AID - 10.1111/pim.12632 [doi] PST - ppublish SO - Parasite Immunol. 2019 Aug;41(8):e12632. doi: 10.1111/pim.12632. Epub 2019 Jun 27.