Early Intracellular Trafficking of Granulibacter bethesdensis in Human Macrophages
Early Intracellular Trafficking of Granulibacter bethesdensis in Human Macrophages
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DOI：
10.1128/iai.00847-16
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发表时间：
2017-06-01
影响因子：
3.1
通讯作者：
Gallin, John I.
中科院分区：
文献类型：
--
作者：
Chu, Jessica;Smelkinson, Margery G.;Gallin, John I.
贝塞登颗粒杆菌是一种革兰氏阴性细菌，感染慢性肉芽肿病（CGD）患者，CGD是一种原发性免疫缺陷，标志是吞噬细胞NADPH氧化酶NOX 2的缺陷。以往的研究表明，NOX 2对G.嗜中性粒细胞和单核细胞的Bethesdense和单核细胞衍生的巨噬细胞（MDM）的抑菌活性需要NOX 2和γ干扰素（IFN-γ）预处理。确定G. bethesdensis逃避吞噬溶酶体杀伤，宿主防御途径在正常和CGD MDM中都是完整的，或者它是否在CGD MDM中占据了不同的细胞内生态位，我们评估了这种生物体的运输模式。我们观察到G. Bethesdense与早期内体抗原1（EEA 1）阳性隔室，随后与溶酶体相关膜蛋白1（LAMP 1）阳性和LysoTracker阳性晚期吞噬体共定位;这些特征在正常和CGD MDM中相似。尽管定位于酸化的晚期吞噬体，活G。从存活的MDM中回收的Bethesdensis细胞的数量大于感染后6天的初始输入。G. Bethesdensis在整个6天的时间过程中保持在膜结合隔室中，并且在某些情况下似乎分裂。这些发现表明，这种生物体抵抗人类巨噬细胞的氧依赖性和氧非依赖性吞噬溶酶体抗菌系统。
Granulibacter bethesdensis is a Gram-negative bacterium that infects patients with chronic granulomatous disease (CGD), a primary immunodeficiency marked by a defect in NOX2, the phagocyte NADPH oxidase. Previous studies have shown that NOX2 is essential for killing of G. bethesdensis by neutrophils and monocytes and that the bacteriostatic activity of monocyte-derived macrophages (MDM) requires NOX2 and gamma interferon (IFN-gamma) pretreatment. To determine whether G. bethesdensis evades phagolysosomal killing, a host defense pathway intact in both normal and CGD MDM, or whether it occupies a distinct intracellular niche in CGD MDM, we assessed the trafficking patterns of this organism. We observed colocalization of G. bethesdensis with an early endosome antigen 1 (EEA1)-positive compartment, followed by colocalization with lysosome-associated membrane protein 1 (LAMP1)positive and LysoTracker-positive late phagosomes; these characteristics were similar in both normal and CGD MDM. Despite localization to acidified late phagosomes, viable G. bethesdensis cells were recovered from viable MDM in numbers greater than in the initial input up to 6 days after infection. G. bethesdensis remains, and in some cases appears to divide, within a membrane-bound compartment for the entire 6-day time course. These findings indicate that this organism resists both oxygendependent and oxygen-independent phagolysosomal antimicrobial systems of human macrophages.