The Crohn's disease-associated adherent-invasive Escherichia coli strain LF82 replicates in mature phagolysosomes within J774 macrophages
The Crohn's disease-associated adherent-invasive Escherichia coli strain LF82 replicates in mature phagolysosomes within J774 macrophages
复制标题
DOI：
10.1111/j.1462-5822.2005.00639.x
复制
发表时间：
2006-03-01
影响因子：
3.4
通讯作者：
Darfeuille-Michaud, A
中科院分区：
文献类型：
--
作者：
Bringer, MA;Glasser, AL;Darfeuille-Michaud, A
从克罗恩病患者中分离出的粘附-侵袭性大肠杆菌（AIEC）能够在大液泡中的巨噬细胞内广泛复制。AIEC细菌在吞噬细胞内存活的机制尚不清楚。本报告描述了含AIEC lf82的吞噬体在J774巨噬细胞内的成熟过程。含LF82的吞噬体通过内吞途径进行运输，这可以通过EEA1和Rab7的顺序获取和丢失以及Lamp-1， Lamp-2和组织蛋白酶d的积累来证明。我们证明，AIEC含LF82的吞噬体在细菌暴露于低pH和组织蛋白酶d的降解活性下成熟为活跃的吞噬溶酶体。最后，我们表明酸性环境是AIEC LF82细菌在J774巨噬细胞内复制所必需的。因此，有证据表明AIEC LF82细菌不会从内吞途径中逃脱，而是与宿主膜细胞器进行正常的相互作用，并在酸性和组织蛋白酶d阳性的空泡吞噬溶酶体中进行复制。
Adherent-invasive Escherichia coli (AIEC) bacteria isolated from Crohn's disease patients are able to extensively replicate within macrophages in large vacuoles. The mechanism by which AIEC bacteria survive within phagocytic cells is unknown. This report describes the maturation of AIEC LF82-containing phagosomes within J774 macrophages. LF82-containing phagosomes traffic through the endocytic pathway as shown by the sequential acquisition and loss of EEA1 and Rab7 and by accumulation of Lamp-1, Lamp-2 and cathepsin D. We demonstrated that AIEC LF82-containing phagosomes mature into active phagolysosomes where bacteria are exposed to low pH and to the degradative activity of cathepsin D. Finally, we showed that an acidic environment is necessary for replication of AIEC LF82 bacteria within J774 macrophages. Thus, evidence is provided that AIEC LF82 bacteria do not escape from the endocytic pathway but undergo normal interaction with host endomembrane organelles and replicate within acidic and cathepsin D-positive vacuolar phagolysosomes.