Geraldino Thais Herrero, de Vito Eliana, Custódio Luiz Antonio, Conchon-Costa Ivete, Gaziri Luis Carlos Jabur, Felipe Ionice, Loyola Wagner, Bonifácio Kamila Landucci
Department of Pathological Sciences, Londrina State University, Londrina, Brazil.
FEMS Immunol Med Microbiol. 2010 Jun 1;59(1):11-7. doi: 10.1111/j.1574-695X.2010.00655.x. Epub 2010 Jan 22.
In a previous study, our group verified that mice pretreated with concanavalin-A (Con-A) produced more tumour necrosis factor (TNF)-alpha and presented greater Candida clearance from the peritoneal cavity, liver and spleen, which yielded a higher survival rate than control animals. In this work, the hypothesis that macrophages were of crucial importance in overcoming the infection was tested. Thus, peritoneal macrophages from mice pretreated for 3 days with Con-A or phosphate-buffered saline (PBS) were coincubated with CR1, CR15 and 577 isolates of Candida albicans for 0.5, 1 and 2 h. The ability of Con-activated macrophages to produce TNF-alpha, ingest via mannose receptors and kill all the isolates was significantly greater compared with PBS-treated macrophages, and activated macrophages exhibited a lower incidence of apoptosis, verified by binding to annexin V-fluorescein isothiocyanate. The transition of yeast cells to filamentous forms during coincubation for 2 h with control macrophages was about 73-80%, whereas in the presence of Con-A-activated macrophages, it was 35-40%. Our results suggest that a greater clearance of C. albicans infection through treatment with Con-A is probably due to the activation of macrophages, which produce more TNF-alpha, express more mannose receptors and are better endowed to kill ingested C. albicans.
在之前的一项研究中,我们的团队证实,用伴刀豆球蛋白A(Con-A)预处理的小鼠产生了更多的肿瘤坏死因子(TNF)-α,并且从腹腔、肝脏和脾脏清除白色念珠菌的能力更强,其存活率高于对照动物。在这项工作中,对巨噬细胞在克服感染中起关键作用这一假设进行了检验。因此,将用Con-A或磷酸盐缓冲盐水(PBS)预处理3天的小鼠的腹腔巨噬细胞与白色念珠菌的CR1、CR15和577分离株共同孵育0.5、1和2小时。与用PBS处理的巨噬细胞相比,Con激活的巨噬细胞产生TNF-α、通过甘露糖受体摄取和杀死所有分离株的能力明显更强,并且通过与膜联蛋白V-异硫氰酸荧光素结合验证,激活的巨噬细胞凋亡发生率更低。与对照巨噬细胞共同孵育2小时期间,酵母细胞向丝状形式的转变约为73-80%,而在存在Con-A激活的巨噬细胞的情况下,这一比例为35-40%。我们的结果表明,通过Con-A治疗实现对白色念珠菌感染的更大清除可能是由于巨噬细胞的激活,其产生更多的TNF-α,表达更多的甘露糖受体,并且更有能力杀死摄入的白色念珠菌。