Interactions of Attenuated Mycobacterium tuberculosis phoP Mutant with Human Macrophages
Interactions of Attenuated Mycobacterium tuberculosis phoP Mutant with Human Macrophages
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DOI：
10.1371/journal.pone.0012978
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发表时间：
2010-09-24
期刊：
影响因子：
3.7
通讯作者：
Martin, Carlos
中科院分区：
文献类型：
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作者：
Ferrer, Nadia L.;Gomez, Ana B.;Martin, Carlos
背景：来自临床分离株的结核分枝杆菌Phop突变体SO2在小鼠骨髓来源的巨噬细胞和体内感染模型中显示出减毒作用，并显示出作为结核病减毒疫苗候选者的高潜力。方法/主要研究结果：在本研究中，我们分析了SO2在人巨噬细胞中的黏附和细胞内生长和运输。我们的结果表明，与野生型菌株相比，单核细胞来源的巨噬细胞和人细胞系THP-1对吞噬细胞的粘附性增强，SO2的细胞内复制受到损害，这与小鼠模型一致。人THP-1细胞的细胞内转运分析表明，巨噬细胞内SO2的减弱可能是由于与亲本结核分枝杆菌株相比，阻止吞噬小体-溶酶体融合的能力减弱。SO2与野生型结核分枝杆菌感染的巨噬细胞释放一氧化氮和分枝杆菌对一氧化氮(NO)的敏感性无差异。结论/意义：SO2具有增强人巨噬细胞结合能力，细胞内转运能力不同于野生型结核分枝杆菌。讨论了Phop突变体SO2的脂谱表达的改变以及它不能分泌ESAT-6。
Background: Mycobacterium tuberculosis phoP mutant SO2 derived from a clinical isolate was shown to be attenuated in mouse bone marrow-derived macrophages and in vivo mouse infection model and has demonstrated a high potential as attenuated vaccine candidate against tuberculosis.Methodology/Principal Findings: In this study, we analyze the adhesion and the intracellular growth and trafficking of SO2 in human macrophages. Our results indicate an enhanced adhesion to phagocitic cells and impaired intracellular replication of SO2 in both monocyte-derived macrophages and human cell line THP-1 in comparison with the wild type strain, consistent with murine model. Intracellular trafficking analysis in human THP-1 cells suggest that attenuation of SO2 within macrophages could be due to an impaired ability to block phagosome-lysosome fusion compared with the parental M. tuberculosis strain. No differences were found between SO2 and the wild-type strains in the release and mycobacterial susceptibility to nitric oxide (NO) produced by infected macrophages.Conclusions/Significance: SO2 has enhanced ability to bind human macrophages and differs in intracellular trafficking as to wild-type M. tuberculosis. The altered lipid profile expression of the phoP mutant SO2 and its inability to secrete ESAT-6 is discussed.