Jiangsu Key Laboratory of Zoonosis, Yangzhou University, No. 48 Wenhui East Road, Yangzhou, 225009, Jiangsu, China.
Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agrifood Safety and Quality, MOA of China, Yangzhou University, Yangzhou, China.
BMC Immunol. 2018 Jun 25;19(1):19. doi: 10.1186/s12865-018-0258-8.
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(Mtb)感染的控制需要 CD4 T 细胞应答和主要组织相容性复合体 II 类(MHC II)呈递 Mtb 抗原(Ag)。树突状细胞(DC)是最强的 Ag 呈递细胞,是启动 T 细胞免疫应答的核心。大量研究表明,DC 在早期感染时间点的抗分枝杆菌免疫应答中发挥重要作用,但这些细胞在这些事件中 Ag 呈递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 对牛分枝杆菌卡介苗(BCG)Ag85A 蛋白的早期 Ag 呈递的体内动力学。结果表明,牛分枝杆菌 BCG Ag85A 蛋白在体内诱导的小鼠 DC 的早期 Ag 呈递活性是短暂的,在 4 h 时出现,在 72 h 时几乎检测不到。CIITA、MHC II 的转录水平和细胞表面 MHC II 分子的表达在 BCG 感染后增加。此外,发现 BCG 存活于腹股沟 LN DC 池内,代表持续的分枝杆菌 Ag85A 蛋白来源,LN DC 与 Ag85A 肽-MHCII 复合物在体内形成。
我们的结果表明,Ag 加工到 MHC II 类分子的抑制导致 Ag85A 肽产生减少,这在很大程度上导致了体内 BCG 感染时 LN DC 呈递 Ag 的持续时间短。