Lung Epithelial Signaling Mediates Early Vaccine-Induced CD4(+) T Cell Activation and Mycobacterium tuberculosis Control.
Lung Epithelial Signaling Mediates Early Vaccine-Induced CD4(+) T Cell Activation and Mycobacterium tuberculosis Control.
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DOI：
10.1128/mbio.01468-21
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发表时间：
2021-08-31
期刊：
影响因子：
6.4
通讯作者：
Khader SA
中科院分区：
文献类型：
--
作者：
Das S;Marin ND;Esaulova E;Ahmed M;Swain A;Rosa BA;Mitreva M;Rangel-Moreno J;Netea MG;Barreiro LB;Divangahi M;Artyomov MN;Kaushal D;Khader SA
结核病（TB）是由单一传染源导致死亡的主要原因之一。迫切需要开发一种结核疫苗，诱导对结核分枝杆菌（Mtb）感染的持久和有效的免疫力。在M中可以诱导早期和上级Mtb控制。牛卡介苗（BCG）接种宿主的先天性免疫应答，以产生有效的疫苗诱导免疫。在本研究中，我们表明，先天性激活的DC是至关重要的粘膜定位克隆激活的疫苗诱导的CD 4 + T细胞在肺和优越的上级早期结核病控制。此外，本研究还揭示了Th 1/Th 17细胞因子轴在上级疫苗诱导的免疫应答中起重要作用。我们的研究还表明，肺上皮细胞中活化B细胞核因子κ-轻链增强子（NF-κβ）通路的活化对于活化疫苗诱导的CD 4 + T细胞的粘膜定位至关重要，以快速控制Mt B。因此，我们的研究为免疫机制提供了新的见解，可以克服结核病疫苗的瓶颈，并提供早期快速结核病控制。
Tuberculosis (TB) is one of the leading causes of death due to a single infectious agent. The development of a TB vaccine that induces durable and effective immunity to Mycobacterium tuberculosis (Mtb) infection is urgently needed. Early and superior Mtb control can be induced in M. bovis Bacillus Calmette-Guérin (BCG)-vaccinated hosts when the innate immune response is targeted to generate effective vaccine-induced immunity. In the present study, we show that innate activation of DCs is critical for mucosal localization of clonally activated vaccine-induced CD4+ T cells in the lung and superior early Mtb control. In addition, our study reveals that Th1/Th17 cytokine axis play an important role in superior vaccine-induced immunity. Our studies also show that activation of the nuclear factor kappa-light-chain enhancer of activated B cell (NF-κβ) pathway in lung epithelial cells is critical for the mucosal localization of activated vaccine-induced CD4+ T cells for rapid Mtb control. Thus, our study provides novel insights into the immune mechanisms that can overcome TB vaccine bottlenecks and provide early rapid Mtb control.