Role of lipids in killing mycobacteria by macrophages: evidence for NF-κB-dependent and -independent killing induced by different lipids
Role of lipids in killing mycobacteria by macrophages: evidence for NF-κB-dependent and -independent killing induced by different lipids
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DOI：
10.1111/j.1462-5822.2008.01263.x
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发表时间：
2009-03-01
影响因子：
3.4
通讯作者：
Griffiths, Gareth
中科院分区：
文献类型：
--
作者：
Gutierrez, Maximiliano Gabriel;Gonzalez, Alexis Perez;Griffiths, Gareth
我们已经证明，几种脂质可以调节巨噬细胞对分枝杆菌的先天免疫反应，并增强它们的杀伤能力。由于NF-kappa B是杀死分枝杆菌所必需的，我们测试了脂质在未感染的巨噬细胞和感染分枝杆菌的巨噬细胞中激活NF-kappa B的能力。在未感染的细胞中，鞘磷脂（SM）、磷脂酰肌醇-4-磷酸（PIP）和花生四烯酸（AA）增强NF-kappa B的激活和细胞表面CD69的表达，CD69是一种由NF-kappa B调节的巨噬细胞激活标志物。鞘磷脂（Sph）、鞘磷脂-1-磷酸（S1P）、二酰基甘油（DAG）、二十碳五烯酸（EPA）和磷脂酰胆碱（PC）不能激活NF-kappa B或CD69。神经酰胺（Cer）激活CD69表达，而不激活NF-kappa B。在污垢分枝杆菌感染的细胞中，NF-kappa B以SM、PIP和AA增强的方式被短暂激活。而鸟分枝杆菌则主要抑制NF-kappa B的激活，只有SM和AA能诱导NF-kappa B的部分激活。而在未感染细胞中激活NF-kappa B的脂质倾向于杀死巨噬细胞中的分枝杆菌，在大多数情况下，Sph和S1P不能激活NF-kappa B，但却能增强对污垢分枝杆菌、鸟分枝杆菌和结核分枝杆菌H37Rv的杀伤。我们的研究结果表明，nf - κ b依赖性和非依赖性机制都参与了巨噬细胞对分枝杆菌的杀伤，并且这两种机制都可以通过选定的脂质来增强。
We have shown that several lipids can modulate the macrophage innate immune response against mycobacteria and enhance their killing. Since NF-kappa B is required for mycobacterial killing, we tested the ability of lipids to activate NF-kappa B in uninfected macrophages and those infected with mycobacteria. In uninfected cells, sphingomyelin (SM), phosphatidylinositol-4-phosphate (PIP) and arachidonic acid (AA) enhanced NF-kappa B activation and the cell surface expression of CD69, a macrophage activation marker regulated by NF-kappa B. Sphingosine (Sph), sphingosine-1-phosphate (S1P), diacylglycerol (DAG), eicosapentanoic acid (EPA) and phosphatidyl choline (PC) failed to activate either NF-kappa B or CD69. Ceramide (Cer) activated CD69 expression without activating NF-kappa B. In Mycobacterium smegmatis-infected cells, NF-kappa B was transiently activated in a manner that was enhanced by SM, PIP and AA. In contrast Mycobacterium avium mostly repressed NF-kappa B activation and only SM and AA could induce its partial activation. While lipids that activate NF-kappa B in uninfected cells tend to kill mycobacteria in macrophages Sph and S1P failed to activate NF-kappa B under most conditions but nevertheless enhanced killing of M. smegmatis, M. avium and M. tuberculosis H37Rv. Our results argue that both NF-kappa B-dependent and -independent mechanisms are involved in macrophage killing of mycobacteria and that both mechanisms can be enhanced by selected lipids.