pCramoll therapy decreases mortality and fungal burden in immunosuppressed mice infected with Cryptococcusgattii.

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.