Rapid loss of early antigen-presenting activity of lymph node dendritic cells against Ag85A protein following Mycobacterium bovis BCG infection.

Rapid loss of early antigen-presenting activity of lymph node dendritic cells against Ag85A protein following Mycobacterium bovis BCG infection.
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牛分枝杆菌 BCG 感染后,淋巴结树突状细胞针对 Ag85A 蛋白的早期抗原呈递活性迅速丧失

DOI:
10.1186/s12865-018-0258-8
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发表时间:
2018-06-25
期刊:
影响因子:
3
通讯作者:
Jiao X
Jiao X
中科院分区:
医学4区
文献类型:
--
作者:
Xu Z;Xia A;Li X;Zhu Z;Shen Y;Jin S;Lan T;Xie Y;Wu H;Meng C;Sun L;Yin Y;Chen X;Jiao X

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结核分枝杆菌 (Mtb) 感染的控制需要 CD4+ T 细胞反应和 Mtb 抗原 (Ag) 的主要组织相容性复合体 II 类 (MHC II) 呈递。树突状细胞 (DC) 是最有效的 Ag 呈递细胞,对于 T 细胞免疫反应的启动至关重要。许多研究表明,DC 在早期感染时间点的抗分枝杆菌免疫反应中发挥着重要作用,但这些细胞在这些事件期间呈递 Ag 的动力学尚不完全清楚。在本研究中,我们评估了小鼠淋巴结 (LN) DC 响应牛分枝杆菌卡介苗 (BCG) Ag85A 蛋白的早期 Ag 呈递的体内动力学。结果表明,牛支原体BCG Ag85A蛋白在体内诱导的小鼠DC的早期Ag提呈活性是短暂的,在4 h时出现,在72 h时几乎检测不到。 BCG感染后CIITA、MHC II的转录水平和细胞表面MHC II分子的表达增加。此外,发现 BCG 在腹股沟 LN DC 库中存活,代表分枝杆菌 Ag85A 蛋白的持续来源,LN DC 与该蛋白在体内形成 Ag85A 肽-MHCII 复合物。我们的结果表明,由于 Ag 加工的抑制而导致 Ag85A 肽产量的减少,这在很大程度上是 BCG 感染体内 LN DC 呈递 Ag 的时间较短的原因。
Control of Mycobacterium tuberculosis (Mtb) infection requires CD4+ T-cell responses and major histocompatibility complex class II (MHC II) presentation of Mtb antigens (Ags). Dendritic cells (DCs) are the most potent of the Ag-presenting cells and are central to the initiation of T-cell immune responses. Much research has indicated that DCs play an important role in anti-mycobacterial immune responses at early infection time points, but the kinetics of Ag presentation by these cells during these events are incompletely understood. In the present study, we evaluated in vivo dynamics of early Ag presentation by murine lymph-node (LN) DCs in response to Mycobacterium bovis bacillus Calmette–Guérin (BCG) Ag85A protein. Results showed that the early Ag-presenting activity of murine DCs induced by M. bovis BCG Ag85A protein in vivo was transient, appearing at 4 h and being barely detectable at 72 h. The transcription levels of CIITA, MHC II and the expression of MHC II molecule on the cell surface increased following BCG infection. Moreover, BCG was found to survive within the inguinal LN DC pool, representing a continuing source of mycobacterial Ag85A protein, with which LN DCs formed Ag85A peptide-MHCII complexes in vivo. Our results demonstrate that a decrease in Ag85A peptide production as a result of the inhibition of Ag processing to is largely responsible for the short duration of Ag presentation by LN DCs during BCG infection in vivo.
结核分枝杆菌对抗原呈递的调节:Toll 样受体的作用。
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发表时间: 2010-04
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