Schistosoma heamatobium tetraspanins TSP-2 and TSP-6 induce Dendritic Cells maturation, cytokine production and T helper cells differentiation in vitro

Urogenital schistosomiasis caused by Schistosoma haematobium is a major cause of disability in endemic areas. Despite its socio-economic burden, no vaccine exists and the parasite's immunobiology remains underexplored. Genome annotation has revealed over 40 different genes encoding tetraspanins...

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Detalles Bibliográficos
Autores: Silvano, Angela, Sotillo, Javier, Cecchi, Marta, Loukas, Alex, Ouedraogo, Mireille, Parenti, Astrid, Bruschi, Fabrizio, Torcia, Maria Gabriella, Mangano, Valentina D
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/26724
Acceso en línea:https://hdl.handle.net/20.500.12105/26724
Access Level:acceso abierto
Palabra clave:Cytokines
Dendritic cells
Immunology
SH-TSP-2
Schistosoma haematobium
Schistosomiasis
T helper cells
Tetraspanins
Animals
Antigens, Helminth
Cell Differentiation
Cells, Cultured
Dendritic Cells
Helminth Proteins
Humans
Descripción
Sumario:Urogenital schistosomiasis caused by Schistosoma haematobium is a major cause of disability in endemic areas. Despite its socio-economic burden, no vaccine exists and the parasite's immunobiology remains underexplored. Genome annotation has revealed over 40 different genes encoding tetraspanins, transmembrane proteins with known immunomodulatory properties in other plathelminthes. This study investigated the role of Sh-TSP-2, Sh-TSP-6 and Sh-TSP-23, which are expressed in the parasite's tegument and extracellular vesicles (EVs). Immature dendritic cells (DCs) from unexposed healthy donors were stimulated with these proteins to evaluate maturation maker expression and cytokine production. Also, pre-activated T CD4 cells were stimulated with the DCs supernatant to assess cytokine gene expression. Sh-TSP-2 and Sh-TSP-6 induced maturation markers and cytokine production in DCs: Sh-TSP-2 increased CD80 and CD83 levels and the concentration of both pro-inflammatory (IL-6, TNF) and regulatory (IL-10) cytokines, while Sh-TSP-6 increased the production of IL-6. Moreover, supernatants from Sh-TSP-2 stimulated DCs induced the expression of Th1 (IFNɣ) and regulatory (IL-10) cytokines in CD4 T cells, while Sh-TSP-6 induced Th2 (IL-4, IL-13) cytokine expression. These results provide evidence that S. haematobium tetraspanins modulate the response of human DCs and CD4 T cells in vitro, and support Sh-TSP-2 as a promising vaccine candidate.