Coexpression of human perforin improves yeast-mediated delivery of DNA and mRNA to mammalian antigen-presenting cells.

Previous studies underlined the capacity of recombinant yeast as efficient vehicle for the targeted delivery of functional nucleic acids as well as proteinaceous antigens to mammalian antigen-presenting cells (APCs). To improve this yeast-mediated cargo transport into APCs, we investigated the impact of coexpression of the human membrane-perturbing protein perforin in comparison with bacterial listeriolysin O (LLO) on the yeast-based delivery of DNA, mRNA and proteins to mammalian APCs. In contrast to LLO, a cholesterol-dependent pore-forming toxin of Listeria, intracellular expression of human perforin in Saccharomyces cerevisiae had no impact on yeast cell viability, while its coexpression significantly increased translocation of ovalbumin and subsequent activation of ovalbumin-specific T lymphocytes.

Candida species fail to produce the immunosuppressive secondary metabolite gliotoxin in vitro.

Yeasts of the genus Candida are a major cause of morbidity and mortality in immunocompromised patients. Despite new insights in recent years, the pathogenesis of Candida infection is still incompletely understood. Previous studies have suggested that gliotoxin, a secondary fungal metabolite with well-known immunosuppressive effects, is produced by various species of the genus Candida, and a possible role of gliotoxin as a virulence factor of C.

Deletion of the gliP gene of Aspergillus fumigatus results in loss of gliotoxin production but has no effect on virulence of the fungus in a low-dose mouse infection model.

Gliotoxin is a secondary metabolite produced by several fungi including the opportunistic human pathogen Aspergillus fumigatus. As gliotoxin exerts immunosuppressive effects in vitro and in vivo, a role as a virulence determinant in invasive aspergillosis has been discussed for a long time but evidence has not been provided until now. Here, by the use of different selection marker genes A.

Identification of a cross-reactive HLA-DRB1*0301-restricted CD4 T cell response directed against cholesterol-binding cytolysins from two different pathogens.

Cholesterol-binding cytolysins constitute an evolutionarily conserved family of pore-forming proteins expressed by different gram-positive pathogens. Listeriolysin O, one well-characterized member of the cytolysin family, is also known to induce specific CD4 and CD8 T cell responses upon infection of mice with Listeria monocytogenes. Here we describe an HLA-DRB1*0301-restricted listeriolysin O-derived T cell epitope that is conserved among several members of the cytolysin family.