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pCramoll therapy decreases mortality and fungal burden in immunosuppressed mice infected with Cryptococcusgattii
Jannyson José Braz Jandú1, Marliete Carvalho da Costa2, Elenildo Dário da Silva Júnior1
1Departamento de Bioquímica, Universidade Federal de Pernambuco, Pernambuco, Brazil.
Abstract:
Cryptococcosis is an infectious disease caused mainly by two species Cryptococcus neoformans and C. gattii, and presents a myriad of symptoms and courses with pulmonary and central nervous system (CNS) clinical manifestations. The infection occurs mainly in immunosuppressed individuals, but C. gattii infections has garnered attention due to its prevalence among seemingly healthy individuals. The main treatment consolidated is lipid formulation amphotericin B plus 5-flucytosine, used on moderate-to-severe pulmonary and disseminated infection, followed by fluconazole. Fluconazole is used for mild-to-moderate pulmonary infection, but resistance phenomena have improved the focus on the search for new antimicrobials and immunoregulatory agents. The purpose of this work is analyze the use of pCramoll, an immunomodulatory lectin obtained from seeds of Cratylia mollis Mart [an endemic plant of Caatinga (Northeastern Brazil semi-arid area)], as therapy against the cryptococcosis in infected mice under iatrogenic immunosuppression by 200 mg/kg cyclophosphamide and 150 mg/kg of 5-fluorouracil association. We observed that the immunosuppression promotes susceptibility to C. gattii infection (Graphical Abstract), resulting in a reduction of 21 days median of mice survival, and an increase in the lung fungal burden at the seventh- and forty-day post-infection. With 1 μg/animal/day pCramoll treatment, the immunosuppressed mice exhibited less fungal burden on the lungs and brain, and were observed to have an increase of 100 % in their survival rate (Graphical Abstract). This work shows for the first time the use of plant lectins as possible immunoregulatory tools in immunosuppressed animals infected with C. gattii.
Insights
This study investigated pCramoll, a plant lectin, as a therapy for Cryptococcus gattii infections in immunosuppressed mice. pCramoll significantly increased survival rates and reduced fungal burden, showing potential as an immunoregulatory agent.
Area of Science:
- Mycology
- Immunology
- Pharmacology
Background:
- Cryptococcosis, caused by Cryptococcus neoformans and Cryptococcus gattii, presents diverse clinical manifestations, primarily affecting the central nervous system and lungs.
- While often seen in immunocompromised individuals, Cryptococcus gattii infections are increasingly noted in healthy populations.
- Current treatments like amphotericin B and fluconazole face challenges due to emerging resistance, necessitating novel therapeutic strategies.
Purpose of the Study:
- To evaluate the efficacy of pCramoll, an immunomodulatory lectin from Cratylia mollis, as a therapeutic agent against Cryptococcus gattii infection.
- To assess the impact of pCramoll on survival rates and fungal burden in a murine model of iatrogenic immunosuppression.
Main Methods:
- Mice were rendered immunosuppressed using a combination of cyclophosphamide and 5-fluorouracil.
- Infected mice received daily treatment with 1 μg/animal/day of pCramoll.
- Fungal burden in the lungs and brain, as well as median survival time, were assessed post-infection.
Main Results:
- Iatrogenic immunosuppression significantly increased susceptibility to Cryptococcus gattii, reducing median survival by 21 days and elevating fungal lung burden.
- pCramoll treatment (1 μg/animal/day) in immunosuppressed mice led to a 100% increase in survival rate.
- Immunomodulatory therapy with pCramoll resulted in decreased fungal loads in the lungs and brain of infected mice.
Conclusions:
- Plant-derived lectins, such as pCramoll, demonstrate potential as immunoregulatory agents for treating opportunistic fungal infections.
- pCramoll shows promise as a novel therapeutic candidate for cryptococcosis, particularly in immunocompromised patients.
- This study highlights the first use of plant lectins as immunomodulatory tools in experimental Cryptococcus gattii infection in immunosuppressed animals.
