Impact of Mycobacterium tuberculosis RD1-locus on human primary dendritic cell immune functions.
Impact of Mycobacterium tuberculosis RD1-locus on human primary dendritic cell immune functions.
复制标题
DOI：
10.1038/srep17078
复制
发表时间：
2015-11-25
影响因子：
4.6
通讯作者：
Coccia EM
中科院分区：
文献类型：
--
作者：
Etna MP;Giacomini E;Pardini M;Severa M;Bottai D;Cruciani M;Rizzo F;Calogero R;Brosch R;Coccia EM
开发针对结核分枝杆菌（Mtb）的疫苗的现代策略旨在改进当前的卡介苗（BCG）疫苗或减弱Mtb疫苗候选物的毒力。在本研究中，在人原代树突状细胞（DC）中研究了野生型或突变的差异1区（RD 1）变体对Mtb和BCG重组体免疫原性的影响。转录组，信号通路的激活，成熟，凋亡，细胞因子的产生和能力，以促进Th 1反应的比较分析表明，DC感RD 1编码的因子ESAT 6和CFP 10的表达的定量和定性差异-BCG或结核分枝杆菌背景。与BCG感染的对应物相比，BCG：：RD 1攻击的DC促进产生IFN-γ的T细胞的扩增。虽然Mtb重组体作为一个强大的Th-1促进刺激，即使与RD 1缺失，减毒Mtb菌株携带的C-末端截短的ESAT-6引起了一个强大的Th-1促进表型在DC。总的来说，这些研究表明RD 1基因座在促进DC免疫调节功能中具有必要但不充分的作用。可能需要额外的分枝杆菌因子来赋予DC高Th 1极化能力，这是成功控制Mtb感染的理想属性。
Modern strategies to develop vaccines against Mycobacterium tuberculosis (Mtb) aim to improve the current Bacillus Calmette-Guerin (BCG) vaccine or to attenuate the virulence of Mtb vaccine candidates. In the present study, the impact of wild type or mutated region of difference 1 (RD1) variants on the immunogenicity of Mtb and BCG recombinants was investigated in human primary dendritic cells (DC). A comparative analysis of transcriptome, signalling pathway activation, maturation, apoptosis, cytokine production and capacity to promote Th1 responses demonstrated that DC sense quantitative and qualitative differences in the expression of RD1-encoded factors—ESAT6 and CFP10—within BCG or Mtb backgrounds. Expansion of IFN-γ producing T cells was promoted by BCG::RD1-challenged DC, as compared to their BCG-infected counterparts. Although Mtb recombinants acted as a strong Th-1 promoting stimulus, even with RD1 deletion, the attenuated Mtb strain carrying a C-terminus truncated ESAT-6 elicited a robust Th1 promoting phenotype in DC. Collectively, these studies indicate a necessary but not sufficient role for the RD1 locus in promoting DC immune-regulatory functions. Additional mycobacterial factors are likely required to endow DC with a high Th1 polarizing capacity, a desirable attribute for a successful control of Mtb infection.