在急性中枢神经系统感染期间,B细胞不是 stromal 细胞激活的驱动因素
Brendan T Boylan1,2, Mihyun Hwang1, Elyse Brozost1
1Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA.
在冠状病毒感染期间,B细胞及其分子淋巴毒素β (LTβ) 不驱动中枢神经系统 stromal 细胞的激活. 虽然LTβ信号增强了 stromal 激活,但它损害了抗病毒T细胞功能和病毒控制.
科学领域:
- 神经免疫学 神经免疫学
- 传染病免疫学 传染病免疫学
背景情况:
- 中枢神经系统 (CNS) stromal 细胞,包括纤维细胞和内皮细胞,通过粘附分子和化学激素调节免疫细胞的进入.
- 虽然慢性激活会导致三级淋巴体结构 (TLS),但中枢神经系统感染期间的早期 stromal 激活可以支持抗病毒 T 细胞,但驱动因素尚不清楚.
研究的目的:
- 在小鼠冠状病毒 (mCoV) 感染期间调查促进纤维细胞网络和中枢神经系统中抗病毒淋巴细胞积累的信号.
- 检查B细胞和淋巴毒素β (LTβ) 在激活中枢神经系统 stromal 细胞中的作用.
主要方法:
- 使用了一个神经向的小鼠冠状病毒 (mCoV) 感染模型.
- 分析了树突细胞激活标记物 (粘附分子,化学因子),纤维细胞标记物波多普拉宁 (PDPN) 和免疫细胞透.
- 采用B细胞特异性LTβ耗尽 (Mb1-creERT2 x Ltβfl/fl小鼠) 和B细胞耗尽 (抗CD20抗体).
- 评估了LTβ受体 (LTβR) 激进作用和与多I:C.直接激活 stromal 细胞的影响.
主要成果:
- 流体细胞激活标志物和PDPN表达动力学与病毒复制相关.
- 局部化的B细胞和T细胞在PDPN反应区域.
- 无论是B细胞特异性LTβ枯竭还是B细胞枯竭都没有影响病毒控制或免疫细胞招募.
- 长期βR激进作用增加了 stromal 激活标记物,但降低了病毒控制和 T 细胞透到中枢神经系统外围细胞.
- 在LTβ.之前,多I:C诱导的PDPN和化学激素在 stromal 细胞中的表达.
结论:
- 在mCoV感染期间,B细胞衍生的LTβ和B细胞不是中枢神经系统 stromal细胞激活的主要驱动因素.
- 虽然LTβR信号影响着树皮细胞激活 (PDPN,化学酶),但它可能会损害抗病毒T细胞反应和病毒控制.
- 流体细胞集成LTβR信号,但LTβ对保护性抗病毒免疫不必,并且可能有害.
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