Mycobacteria manipulate macrophage recruitment through coordinated use of membrane lipids.
Mycobacteria manipulate macrophage recruitment through coordinated use of membrane lipids.
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结核分枝杆菌是人类结核病（TB）的病因，其进化生存取决于其侵入宿主、复制和传播感染的能力。M.结核病感染巨噬细胞，巨噬细胞将其运送到更深的组织。分枝杆菌如何在这些广泛杀微生物的细胞中生存是一个重要的问题。在这里，我们表明，M。结核病及其致病性近亲海洋分枝杆菌优先招募和感染允许的巨噬细胞，同时逃避杀微生物的巨噬细胞。这种免疫逃避是通过使用细胞表面相关的phthiocerol dimyceroserate（PDIM）脂质来掩盖潜在的病原体相关分子模式（PAMP）来实现的。在不存在PDIM的情况下，这些PAMPs发出巨噬细胞的toll样受体（TLR）依赖性募集信号，巨噬细胞产生杀微生物活性氮物质。一致地，相关的酚糖脂（PGL）通过宿主趋化因子受体2（CCR2）介导的途径促进允许的巨噬细胞的募集。因此，我们已经确定了PDIM的协调作用，已知PDIM对分枝杆菌毒力和PGL是必需的，PGL（沿着CCR2）已知与人TB相关。我们的研究结果也为长期以来的观察提供了一种解释，即M。结核病在下呼吸道的相对无菌环境中而不是在上呼吸道中引发感染，在上呼吸道中，驻留的微生物群落和吸入的环境微生物可以通过TLR依赖性信号传导持续地募集杀微生物巨噬细胞。
The evolutionary survival of Mycobacterium tuberculosis, the cause of human tuberculosis (TB), depends on its ability to invade the host, replicate, and transmit infection. At its initial peripheral infection site in the distal lung airways, M. tuberculosis infects macrophages which transport it to deeper tissues. How mycobacteria survive in these broadly microbicidal cells is an important question. Here we show that M. tuberculosis, and its close pathogenic relative Mycobacterium marinum, preferentially recruit and infect permissive macrophages while evading microbicidal ones. This immune evasion is accomplished by using cell surface associated phthiocerol dimycoceroserate (PDIM) lipids to mask underlying pathogen-associated molecular patterns (PAMPs). In the absence of PDIM, these PAMPs signal a toll-like receptor (TLR)-dependent recruitment of macrophages that produce microbicidal reactive nitrogen species. Concordantly, the related phenolic glycolipids (PGL), promote recruitment of permissive macrophages via a host chemokine receptor 2 (CCR2)-mediated pathway. Thus, we have identified coordinated roles for PDIM, known to be essential for mycobacterial virulence and PGL, which (along with CCR2) is known to be associated with human TB. Our findings also suggest an explanation for the longstanding observation that M. tuberculosis initiates infection in the relatively sterile environment of the lower respiratory tract, rather than in the upper respiratory tract, where resident microflora and inhaled environmental microbes may continually recruit microbicidal macrophages through TLR-dependent signaling.
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DOI：
10.1084/jem.20050126
发表时间：
2005-12-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Flores-Villanueva PO;Ruiz-Morales JA;Song CH;Flores LM;Jo EK;Montaño M;Barnes PF;Selman M;Granados J
通讯作者：
Granados J
DOI：
10.1084/jem.175.4.1111
发表时间：
1992-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chan J;Xing Y;Magliozzo RS;Bloom BR
通讯作者：
Bloom BR
影响因子：
15.9
作者：
Antonelli, Lis R. V.;Rothfuchs, Antonio Gigliotti;Sher, Alan
通讯作者：
Sher, Alan
影响因子：
3.4
作者：
Brannon MK;Davis JM;Mathias JR;Hall CJ;Emerson JC;Crosier PS;Huttenlocher A;Ramakrishnan L;Moskowitz SM
通讯作者：
Moskowitz SM
影响因子：
8.8
作者：
Takaki K;Cosma CL;Troll MA;Ramakrishnan L
通讯作者：
Ramakrishnan L