title: Identification of trans-sialidases as a common mediator of endothelial cell activation by African trypanosomes.
abstract: Understanding African Trypanosomiasis (AT) host-pathogen interaction is the key to an "anti-disease vaccine", a novel strategy to control AT. Here we provide a better insight into this poorly described interaction by characterizing the activation of a panel of endothelial cells by bloodstream forms of four African trypanosome species, known to interact with host endothelium. T. congolense, T. vivax, and T. b. gambiense activated the endothelial NF-κB pathway, but interestingly, not T. b. brucei. The parasitic TS (trans-sialidases) mediated this NF-κB activation, remarkably via their lectin-like domain and induced production of pro-inflammatory molecules not only in vitro but also in vivo, suggesting a considerable impact on pathogenesis. For the first time, TS activity was identified in T. b. gambiense BSF which distinguishes it from the subspecies T. b. brucei. The corresponding TS were characterized and shown to activate endothelial cells, suggesting that TS represent a common mediator of endothelium activation among trypanosome species with divergent physiopathologies.
authors.affiliation: French National Centre for Scientific Research (CNRS), Université Bordeaux Segalen, Microbiologie fondamentale et Pathogénicité, UMR 5234, Bordeaux, France.
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Ammar
authors.forename: Nicolas
authors.initials: N
authors.lastname: Plazolles
authors.forename: Théo
authors.initials: T
authors.lastname: Baltz
authors.forename: Virginie
authors.initials: V
authors.lastname: Coustou
mesh_terms: D000818:Animals; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009439:Neuraminidase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014345:Trypanosoma / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D014353:Trypanosomiasis, African / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000473:pathology
chemical_list: D006023:Glycoproteins; D018836:Inflammation Mediators; D016328:NF-kappa B; D015800:Protozoan Proteins; C069715:trans-sialidase; D009439:Neuraminidase