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

Angela Silvano; Javier Sotillo; Marta Cecchi; Alex Loukas; Mireille Ouedraogo; Astrid Parenti; Fabrizio Bruschi; Maria Gabriella Torcia; Valentina D Mangano

doi:10.1016/j.micinf.2024.105439

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

Microbes Infect. 2024 Nov 15:105439. doi: 10.1016/j.micinf.2024.105439. Online ahead of print.

Authors

Angela Silvano¹, Javier Sotillo², Marta Cecchi³, Alex Loukas⁴, Mireille Ouedraogo⁵, Astrid Parenti¹, Fabrizio Bruschi⁶, Maria Gabriella Torcia⁷, Valentina D Mangano⁸

Affiliations

¹ Dept. of Health Sciences, University of Florence, Florence, Italy.
² Parasitology Reference and Research Laboratory, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
³ Dept. of Health Sciences, University of Florence, Florence, Italy; Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy.
⁴ Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia.
⁵ Dept. of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy; Dep. of Public Health and Infectious Diseases, University of Rome La Sapienza, Italy; Centre National de Recherche et Formation sur le Paludisme, Ouagadougou, Burkina Faso.
⁶ Dept. of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
⁷ Dept. of Clinical and Experimental Medicine, University of Florence, Florence, Italy. Electronic address: maria.torcia@unifi.it.
⁸ Dept. of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy. Electronic address: valentina.mangano@unipi.it.

PMID: 39549890
DOI: 10.1016/j.micinf.2024.105439

Abstract

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.

Keywords: Cytokines; Dendritic cells; Immunology; SH-TSP-2; Schistosoma haematobium; Schistosomiasis; T helper cells; Tetraspanins.