O uso de pCramoll como tratamento da criptococose em camundongos imunocompetentes e imunossurimidos

Historically, infectious diseases are the main causes of mortality and morbidity and reflect in high social and economic impact worldwide. The phenomenon of microbial resistance is an important factor for the high prevalence of these infections, and exponentially reduce the available treatment strategies. In this context, there is an urgent need to search new therapeutic approaches, and the immunotherapy is an effective way of to combat these diseases. In this sense, this work approaches the effect of plant lectins as possible immunomodulatory tools to improve host immune response against pathogenic microorganisms. Cryptococcus gattii is a major infectious agent of cryptococcosis in healthy individuals, but it also affects immunosuppressed individuals. For the treatment of infection, antifungal drugs alone or in combination are used, however, to the toxicity of these drugs and the increasing appearance of resistant strains drives this search for therapies that are efficient. In the literature review, it was observed that in vitro the lectins have antimicrobial and immunoregulatory actions, as well as in experimental models, in vivo, increasing the survival of mice under microbial challenge, either prophylactically or therapeutically. This way, the effect of pCramoll, an immunoregulatory lectin extracted from seeds of Cratylia mollis Mart [endemic plant from Caatinga (Northeastern Semi-arid region)], was demonstrated in a model of intratracheal infection by Crytococcus gattii. In the microbial challenge projected, the infection by C. gattii and the proposed treatments (pCramoll 1ug / dose alone or in association with fluconazole 200 mg.kg-1), were analysed parameters as fungal load in the target organs and quantification in the levels of the inflammatory factors involved in the disease. pCramoll treatment increased in vitro the phagocytosis of C. gattii by marrow macrophages after 3h of incubation, associated with high production of reactive oxygen and nitrogen species, and decreased intracellular fungal proliferation rate. In vivo, pCramoll alone or in combination with fluconazole increased survival and improved morbidity of infected animals, with benefits in aspects such as (neuropsychiatric state, motor behavior, autonomic function, tonus and muscle strength, and reflex / sensory function), modulated the levels of IFN-γ, IL-6, IL-10 and IL-17 and the inflammatory infiltrate during the infectious process. In view of this immunoregulatory potential presented by pCramoll in the fight against cryptococcosis, it was observed the influence of lectin in the treatment of C. gattii infection in mice after iatrogenic immunosuppression under Cyclophosphamide 200 mg.kg-1 and 5 -Fluoroacyl 150 mg.kg-1 combination, the pCramoll therapy reduced the fungal load on the lungs and brains of the animals, and consequently increased survival rate (100% survival) of immunosuppressed animals to compared with immunosuppressed, infected and untreated. Therefore, it was possible to demonstrate that the use of plant lectins such as pCramoll are promising tools in the development of new therapeutic strategies based on immunomodulators in the fight against infectious microorganisms with difficult antimicrobial control such as cryptococcosis agents.