Department of Microbiology and Immunology, Institute of Biosciences of Botucatu, São Paulo State University (UNESP), Botucatu 18618-691, São Paulo, Brazil.
Department of Biological Sciences, School of Sciences, São Paulo State University (UNESP), Bauru 17033-360, São Paulo, Brazil.
Toxins (Basel). 2019 Jul 26;11(8):443. doi: 10.3390/toxins11080443.
Gliotoxin (GTX) is the major and the most potent mycotoxin that is secreted by , which is capable of injuring and killing microglial cells, astrocytes, and oligodendrocytes. During the last years, studies with patients and experimental models of multiple sclerosis (MS), which is an autoimmune disease of the central nervous system (CNS), suggested that fungal infections are among the possible initiators or aggravators of this pathology. The deleterious effect can occur through a direct interaction of the fungus with the CNS or by the toxin release from a non-neurological site. In the present work, we investigated the effect of GTX on experimental autoimmune encephalomyelitis (EAE) development. Female C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein and then intraperitoneally injected with three doses of GTX (1 mg/kg b.w., each) on days 4, 7, and 10. GTX aggravated clinical symptoms of the disease in a dose-dependent way and this outcome was concomitant with an increased neuroinflammation. CNS analyses revealed that GTX locally increased the relative expression of inflammatory genes and the cytokine production. Our results indicate that GTX administered in a non-neuronal site was able to increase neuroinflammation in EAE. Other mycotoxins could also be deleterious to many neurological diseases by similar mechanisms.
曲古抑菌素（GTX）是一种由 分泌的主要且最有效的真菌毒素，能够损伤和杀死小胶质细胞、星形胶质细胞和少突胶质细胞。在过去的几年中，对多发性硬化症（MS）患者和实验模型的研究表明，中枢神经系统（CNS）的自身免疫性疾病，真菌感染是这种病理学的可能引发因素或加重因素之一。这种有害影响可能通过真菌与 CNS 的直接相互作用发生，也可能通过非神经部位的毒素释放发生。在本工作中，我们研究了 GTX 对实验性自身免疫性脑脊髓炎（EAE）发展的影响。雌性 C57BL/6 小鼠用髓鞘少突胶质糖蛋白免疫，然后在第 4、7 和 10 天腹腔内注射三剂 GTX（1mg/kg b.w.，每次）。GTX 以剂量依赖性方式加重了疾病的临床症状，这一结果伴随着神经炎症的增加。中枢神经系统分析表明，GTX 局部增加了炎症基因的相对表达和细胞因子的产生。我们的结果表明，GTX 在非神经部位给药能够增加 EAE 中的神经炎症。其他真菌毒素也可能通过类似的机制对许多神经疾病造成损害。
