Experimental sporotrichosis in a cyclophosphamide-induced immunosuppressed mice model

Abstract

This report describes a model of host resistance for Sporothrix schenckii, an opportunistic fungi in immunosuppressed mice with cyclophosphamide (CY) to be used in studies of immunotoxicology and immunopharmacology. Two doses of CY were administered intraperitoneally: 200 mg/kg and a booster of 150 mg/kg at 9-day intervals. Three days after the first dose of CY the animals were infected subcutaneously with 1.8 × 108 yeast/ml (S. schenckii ATCC 16345). At 7 and 14 days post-infection, the animals were euthanized and analyzed the fungal load by unit forming colony count in the spleen and popliteal lymph nodes. The relative weight of thymus and spleen, splenic index, the frequency of T and B cells in spleen by flow cytometry, the hind paw inflammation index and cytokine (interleukin [IL]-17, IL-10, and interferon [IFN]-γ) profile were measured. Histopathological studies of the spleen and the hind paw were also assessed. The immunosuppression status was confirmed at the evaluated days by reduction of relative weight of thymus, reduction of the splenic white pulp, the population of B and T lymphocytes, and the cytokine profile in the treated mice with CY in comparison with nontreated groups, associated to higher fungal load in hind paw and spleen in the infected mice. The described model reveals an increasing in susceptibility to infection and severity when associated with immunosuppression. This model can serve as a reference for studies of S. schenckii host resistance in pharmaceutical and toxicological studies.

Monitoring Fungal Burden and Viability of Sporothrix spp. in Skin Lesions of Cats for Predicting Antifungal Treatment Response

“…infection in these animals. In fact, experimental models have shown that the efficiency of the immune response will affect the control of fungal burden [ 23 , 24 , 25 , 26 ]. Similarly, in humans and dogs, the occurrence of lesions with high fungal burdens is usually associated with immunosuppressive conditions, such as malnutrition, use of steroid, and the presence of underlying diseases, especially those that induce immunosuppression, such as AIDS [ 27 , 28 , 29 , 30 , 31 , 32 ].…”

Protective Effect of Bergenin against Cyclophosphamide-Induced Immunosuppression by Immunomodulatory Effect and Antioxidation in Balb/c Mice

“…Generally, chemotherapeutics drugs often generate many harmful side effects such as cytotoxic effects and host immunosuppression, no matter how great of their therapeutic effects are [ 4 ]. Cyclophosphamide (Cy), an alkylating agent, has been widely used as chemotherapeutic drug which results in a lot of adverse effects including immunosuppression, bone marrow suppression, leucopenia and oxidative stress [ 5 , 6 , 7 , 8 ]. It has been reported that Cy can generate oxidative stresses, mediate disruption of the redox balance, and lead to biochemical and physiological disturbances [ 9 ].…”

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

“…After inoculation, several mechanisms of the innate immunity are activated to control the infection directly and by stimulating the specific immune response (Carlos et al, 1994;Gonçalves et al, 2015;Ferreira et al, 2015;Maia et al, 2016;Jellmayer et al, 2017). The importance of these immune mechanisms for the control of S. schenckii-infection is evidenced by the higher fungal colonization and dissemination in immunosuppressed mouse models (Manente et al, 2018;Batista-Duharte et al, 2018a) and immunocompromised patients, mainly individuals with HIV-AIDS (Moreira et al, 2015).…”