Mycobacterium tuberculosis Co-operonic PE32/PPE65 Proteins Alter Host Immune Responses by Hampering Th1 Response.
Mycobacterium tuberculosis Co-operonic PE32/PPE65 Proteins Alter Host Immune Responses by Hampering Th1 Response.
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DOI：
10.3389/fmicb.2016.00719
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发表时间：
2016
影响因子：
5.2
通讯作者：
Ehtesham NZ
中科院分区：
文献类型：
--
作者：
Khubaib M;Sheikh JA;Pandey S;Srikanth B;Bhuwan M;Khan N;Hasnain SE;Ehtesham NZ
PE/PPE基因与ESAT-6样基因簇聚在一起，可能与结核分枝杆菌的抗原变异和毒力有关。它们在宿主的免疫逃避和免疫调节中的作用也有很好的记录。我们提出的证据表明，PE 32/PPE 65存在于RD 8区域内的协同操纵，共转录，共翻译，并在调节宿主免疫反应中发挥作用。使用巨噬细胞系的实验表明，这种蛋白质复合物抑制促炎细胞因子如TNF-α和IL-6，同时还诱导抗炎IL-10的高表达。用这些重组蛋白免疫小鼠可减弱有效的Th 1应答，这可从产生IFN-γ和IL-2的CD 4+和CD 8 + T细胞的频率降低得到证实。免疫小鼠血清IgG亚型分析显示，与IgG 2a和IgG 2b相比，IgG 1水平较高。进一步的IgG 1/IgG 2a比率清楚地表明，蛋白质复合物操纵对病原体有利的宿主免疫应答。我们的研究结果表明，共转录和共翻译的PE 32和PPE 65抗原特异性地参与调节抗分枝杆菌宿主免疫应答，通过阻碍Th 1应答。
PE/PPE genes, present in cluster with ESAT-6 like genes, are suspected to have a role in antigenic variation and virulence of Mycobacterium tuberculosis. Their roles in immune evasion and immune modulation of host are also well documented. We present evidence that PE32/PPE65 present within the RD8 region are co-operonic, co-transcribed, and co-translated, and play role in modulating host immune responses. Experiments with macrophage cell lines revealed that this protein complex suppresses pro-inflammatory cytokines such as TNF-α and IL-6 whereas also inducing high expression of anti-inflammatory IL-10. Immunization of mice with these recombinant proteins dampens an effective Th1 response as evident from reduced frequency of IFN-γ and IL-2 producing CD4+ and CD8+ T cells. IgG sub-typing from serum of immunized mice revealed high levels of IgG1 when compared with IgG2a and IgG2b. Further IgG1/IgG2a ratio clearly demonstrated that the protein complex manipulates the host immune response favorable to the pathogen. Our results demonstrate that the co-transcribed and co-translated PE32 and PPE65 antigens are involved specifically in modulating anti-mycobacterial host immune response by hampering Th1 response.