Sporothrix brasiliensis induces a more severe disease associated with sustained Th17 and regulatory T cells responses than Sporothrix schenckii sensu stricto in mice

Abstract

Little is known about the differences in the CD4þ T-cell response induced by Sporothrix schenckii and Sporothrix brasiliensis, the most virulent species that cause sporotrichosis. Here, the helper (Th) and regulatory T cells (Tregs) responses were evaluated comparatively in a murine model of sporotrichosis on days 7, 21 and 35 after subcutaneous infection with either S. schenckii or S. brasiliensis conidia. The fungal load was measured at the site of infection, as well as in the liver and spleen. The Th1/Th17/Tregs responses were analyzed in the spleen, while the level of IL-2, IL-4, IL-6, TNF-alpha, IFN-ɣ, IL-17A and IL-10 cytokines were measured at the local site of infection on 24 h postinfections and in sera on the indicated days. S. brasiliensis caused a longer-lasting infection in the skin and chronic systemic dissemination associated to more severe granulomatous lesions. Similar Th1/Th1-Th17/Tregs responses were induced by both S. brasiliensis and S. schenckii on 7th and 21st d.p.i but on 35 d.p.i a reduction of Th1 and Th1-Th17 cells, associated to higher values of Th17/Tregs cells was observed only in S. brasiliensis-infected mice. In summary, S. brasiliensis caused a more severe disease associated with sustained Th17/Tregs responses than S. schenckii in mice.

Adaptive stress response induced by toluene increasesSporothrix schenckiivirulence and host immune response

“…Several studies reveals that a Th1 and Th17 are stimulated during S. schenckii infection and they are important for the fungal clearance (Ferreira et al ., 2015; Gonçalves et al ., 2017; Batista-Duharte et al ., 2018). Interestingly, a recent report of our group reveled that both S. schenckii and the more virulent S. brasiliensis stimulate similar Th1 response, but S. brasiliensis induced a more severe disease associated with sustained Th17 and a regulatory T cells (Tregs) responses than S. schenckii (Batista-Duharte et al ., 2018). We are developing new analyzes to deepen the immunological mechanisms associated with the greater virulence of the group infected with the fungus exposed to 0.1% of toluene observed in this study.…”

Transcriptome-wide expression profiling of Sporothrix schenckii yeast and mycelial forms and the establishment of the Sporothrix Genome DataBase

“…In the environment, or at 25 °C, they grow as moulds, forming conidia, whereas at 37 °C, or when acquired by humans, they are capable of converting into pathogenic yeasts that effectively overcome the host immune defences and cause disease [7]. Surprisingly, despite their very close phylogenetic relationships, the members of the pathogenic clade showed remarkable differences in many aspects of their basic biology, including epidemiology, antifungal resistance, virulence and pathogenicity [8][9][10][11][12]. Nevertheless, the study of pathogenic Sporothrix species is still mainly limited to their clinical aspects, laboratory diagnosis and therapy [6], and little progress has been made in understanding the genetics and gene regulatory networks that control many biological processes, including dimorphism and the associated saprophytic/pathogenic change.…”

Immunization with recombinant enolase ofSporothrixspp (rSsEno) confers effective protection against sporotrichosis in mice

“…Recently, our group reported a similar result in a model of C57BL6 mice subcutaneously infected with either S. schenckii or S. brasiliensis . However, the higher virulence of S. brasiliensis caused a long-lasting infection associated with severe tissue lesions that stimulated a regulatoryT cell (Tregs) response with deleterious effects on the Th1 and Th1/Th17 response, although a compensatory Th17 response was induced 50 . We also demonstrated in an immunoprophylaxis study in BALB/c mice that either aluminum hydroxide adjuvant or PGA, both formulated with the Ss16345-WCP containing the immunoreactive enolase, induced a Th1, Th2 and Th17 profile, in addition to high stimulation of specific antibodies that conferred protection in these animals after challenge with Ss16345 or Ss250 20 .…”