Immune Response Induced by an Immunodominant 60 kDa Glycoprotein of the Cell Wall ofSporothrix schenckiiin Two Mice Strains with Experimental Sporotrichosis

Abstract

Cell wall (CW) components of fungus Sporothrix schenckii are the major inductors antigens of immune responses. The immunodominant 60 kDa glycoprotein (gp60) has been shown to be associated with the virulence of this fungus but its role in experimental sporotrichosis is unknown. In this work, the immunological effects of CW-purified gp60 were investigated in a model of experimental subcutaneous sporotrichosis in normal and gp60-preimmunized C57BL/6 and BALB/c mice strains which were then infected with S. schenckii conidia. Results showed that both mice strains use different cytokine profiles in order to fight S. schenckii infection; C57BL/6 mice seem to use a Th17 response while BALB/c mice tend to depend on a Th1 profile. Preimmunization with gp60 showed a downregulatory effect on the immune response since cytokines levels were diminished in both strains. There were no significant differences in the magnitude of dorsoplantar inflammation between gp60-preimmunized and nonimmunized mice of both strains. However, skin lesions due to the infection in gp60-preimmunized mice were more severe in BALB/c than in C57BL/6 mice, suggesting that the antigen exerts a higher downregulatory effect on the Th1 response.

Skin Mast Cells Contribute to Sporothrix schenckii Infection

“…To investigate the role of MCs in sporotrichosis, we used a modified mouse model with subcutaneous injections of S. schenckii into the foot pad of mouse (31,32). This model shows many features of skin sporotrichosis in patients including ulceration, scarring, and crusty lesions, as well as nodules at infected skin sites (23,33).…”

“…The molecular mechanisms remain to be investigated and identified. Importantly, other innate immune cells such as macrophages, neutrophils, and dendritic cells have also been described to release TNF and IL-6 in response to S. schenckii infection (32,39). In addition, both HK and Kit W / Wv mice have reduced basophil numbers.…”

Comparative efficacy and toxicity of two vaccine candidates against Sporothrix schenckii using either Montanide™ Pet Gel A or aluminum hydroxide adjuvants in mice

“…As a whole, these studies evidence the protective effect of antigen-specific antibodies against both species. In a recent study, Alba-Fierro et al [38] demonstrated the immunogenicity of an immunodominant 60 kDa glycoprotein from the S. schenckii cell wall and suggested its potential in a vaccine candidate.…”

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

“…In the last two decades, sporotrichosis has been a hyperendemic zoonosis transmitted preferentially by the domestic cat, especially in Brazil. The high incidence of sporotrichiosis together with the ineffectiveness of treatment, especially in immunocompromised individuals, has reinforced the need to identify antigenic targets on the cell surface of species of clinical interest of the genus Sporothrix for immunological prevention and therapeutic intervention 17,34…”

“…However, in immunocompromised patients with neoplastic diseases, transplantation or AIDS, the conventional treatment with classical antifungals is generally ineffective 15,16 . The lack of a veterinary and/or human vaccine against this disease has awakened interest in the identification of S. schenckii cell wall immunoreactive components involved in fungal pathogenesis 17 and the induction of the immune response 18 that can be used for immunoprophylaxis and immunotherapy against sporotrichosis.…”