Jandú Jannyson J, Costa Marliete C, Santos Julliana R A, Andrade Fernanda M, Magalhães Thais F, Silva Márcia V, Castro Maria C A B, Coelho Luanna C B B, Gomes Aline G, Paixão Tatiane A, Santos Daniel A, Correia Maria T S
Departamento de Bioquímica, Universidade Federal de PernambucoRecife, Brazil.
Departamento de Microbiologia, Universidade Federal de Minas GeraisBelo Horizonte, Brazil.
Front Cell Infect Microbiol. 2017 May 24;7:211. doi: 10.3389/fcimb.2017.00211. eCollection 2017.
is one of the main causative agents of cryptococcosis in immunocompetent individuals. Treatment of the infection is based on the use of antimycotics, however, the toxicity of these drugs and the increase of drug-resistant strains have driven the search for more effective and less toxic therapies for cryptococcosis. pCramoll are isolectins purified from seeds of , a native forage plant from Brazil, which has become a versatile tool for biomedical application. We evaluated the effect of pCramoll alone and in combination with fluconazole for the treatment of mice infected with . pCramoll alone or in combination with fluconazole increased the survival, reduced the morbidity and improved mice behavior i.e., neuropsychiatric state, motor behavior, autonomic function, muscle tone and strength and reflex/sensory function. These results were associated with (i) decreased pulmonary and cerebral fungal burden and (ii) increased inflammatory infiltrate and modulatory of IFNγ, IL-6, IL-10, and IL-17A cytokines in mice treated with pCramoll. Indeed, bone marrow-derived macrophages pulsed with pCramoll had increased ability to engulf , with an enhanced production of reactive oxygen species and decrease of intracellular fungal proliferation. These findings point toward the use of pCramoll in combination with fluconazole as a viable, alternative therapy for cryptococcosis management.
是免疫功能正常个体中隐球菌病的主要病原体之一。该感染的治疗基于抗真菌药物的使用,然而,这些药物的毒性以及耐药菌株的增加促使人们寻找更有效且毒性更小的隐球菌病治疗方法。pCramoll是从巴西本土饲料植物的种子中纯化得到的异凝集素,它已成为生物医学应用的一种多功能工具。我们评估了pCramoll单独使用以及与氟康唑联合使用对感染小鼠的治疗效果。单独使用pCramoll或与氟康唑联合使用均可提高生存率、降低发病率并改善小鼠行为,即神经精神状态、运动行为、自主功能、肌张力和力量以及反射/感觉功能。这些结果与以下情况相关:(i)肺部和脑部真菌负荷降低;(ii)用pCramoll治疗的小鼠中炎性浸润增加以及IFNγ、IL - 6、IL - 10和IL - 17A细胞因子的调节。事实上,用pCramoll脉冲处理的骨髓来源巨噬细胞吞噬能力增强,活性氧产生增加,细胞内真菌增殖减少。这些发现表明pCramoll与氟康唑联合使用可作为隐球菌病治疗的一种可行替代疗法。