传统居住条件会减弱实验性自身免疫性脑脊髓炎的发展。
Conventional housing conditions attenuate the development of experimental autoimmune encephalomyelitis.
作者信息
Arndt Andreas, Hoffacker Peter, Zellmer Konstantin, Goecer Oktay, Recks Mascha S, Kuerten Stefanie
机构信息
Department of Anatomy I, University of Cologne, Cologne, Germany.
Department of Anatomy and Cell Biology, University of Wuerzburg, Wuerzburg, Germany.
出版信息
PLoS One. 2014 Jun 11;9(6):e99794. doi: 10.1371/journal.pone.0099794. eCollection 2014.
BACKGROUND
The etiology of multiple sclerosis (MS) has remained unclear, but a causative contribution of factors outside the central nervous system (CNS) is conceivable. It was recently suggested that gut bacteria trigger the activation of CNS-reactive T cells and the development of demyelinative disease.
METHODS
C57BL/6 (B6) mice were kept either under specific pathogen free or conventional housing conditions, immunized with the myelin basic protein (MBP)-proteolipid protein (PLP) fusion protein MP4 and the development of EAE was clinically monitored. The germinal center size of the Peyer's patches was determined by immunohistochemistry in addition to the level of total IgG secretion which was assessed by ELISPOT. ELISPOT assays were also used to measure MP4-specific T cell and B cell responses in the Peyer's patches and the spleen. Ear swelling assays were performed to determine the extent of delayed-type hypersensitivity reactions in specific pathogen free and conventionally housed mice.
RESULTS
In B6 mice that were actively immunized with MP4 and kept under conventional housing conditions clinical disease was significantly attenuated compared to specific pathogen free mice. Conventionally housed mice displayed increased levels of IgG secretion in the Peyer's patches, while the germinal center formation in the gut and the MP4-specific TH17 response in the spleen were diminished after immunization. Accordingly, these mice displayed an attenuated delayed type hypersensitivity (DTH) reaction in ear swelling assays.
CONCLUSIONS
The data corroborate the notion that housing conditions play a substantial role in the induction of murine EAE and suggest that the presence of gut bacteria might be associated with a decreased immune response to antigens of lower affinity. This concept could be of importance for MS and calls for caution when considering the therapeutic approach to treat patients with antibiotics.
背景
多发性硬化症（MS）的病因尚不清楚，但中枢神经系统（CNS）外的因素可能起到致病作用。最近有研究表明，肠道细菌可触发中枢神经系统反应性T细胞的活化及脱髓鞘疾病的发生。
方法
将C57BL/6（B6）小鼠饲养在无特定病原体或常规环境条件下，用髓鞘碱性蛋白（MBP）-蛋白脂蛋白（PLP）融合蛋白MP4进行免疫，并临床监测实验性自身免疫性脑脊髓炎（EAE）的发展情况。除了通过酶联免疫斑点法（ELISPOT）评估总IgG分泌水平外，还通过免疫组织化学法测定派尔集合淋巴结的生发中心大小。ELISPOT分析还用于测量派尔集合淋巴结和脾脏中MP4特异性T细胞和B细胞反应。进行耳部肿胀试验以确定无特定病原体和常规饲养小鼠的迟发型超敏反应程度。
结果
与无特定病原体的小鼠相比，用MP4主动免疫并饲养在常规环境条件下的B6小鼠临床疾病明显减轻。常规饲养的小鼠派尔集合淋巴结中IgG分泌水平升高，而免疫后肠道生发中心形成及脾脏中MP4特异性TH17反应减弱。因此，这些小鼠在耳部肿胀试验中迟发型超敏（DTH）反应减弱。
结论
数据证实了饲养条件在诱导小鼠EAE中起重要作用的观点，并表明肠道细菌的存在可能与对低亲和力抗原的免疫反应降低有关。这一概念可能对MS具有重要意义，在考虑用抗生素治疗患者的治疗方法时需谨慎。
Zotero 插件