The efficiency of the translocation of Mycobacterium tuberculosis across a bilayer of epithelial and endothelial cells as a model of the alveolar wall is a consequence of transport within mononuclear phagocytes and invasion of alveolar epithelial cells

The efficiency of the translocation of Mycobacterium tuberculosis across a bilayer of epithelial and endothelial cells as a model of the alveolar wall is a consequence of transport within mononuclear phagocytes and invasion of alveolar epithelial cells
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DOI:
10.1128/iai.70.1.140-146.2002
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发表时间:
2002-01-01
影响因子:
3.1
通讯作者:
Goodman, J
Goodman, J
中科院分区:
医学2区
文献类型:
--
作者:
Bermudez, LE;Sangari, FJ;Goodman, J

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结核分枝杆菌穿过肺泡壁在肺部建立感染的机制尚不清楚。为了更好地理解易位机制并创建模型来研究细菌穿过肺泡壁的不同阶段,我们建立了两层 Transwell 系统。对结核分枝杆菌 H37Rv 穿过和破坏膜的能力进行了评估。结核分枝杆菌侵入 A549 II 型肺泡细胞的效率为初始接种物的 2% 至 3%,但其侵入内皮细胞的效率不高。然而,侵入 A549 细胞的细菌随后能够被内皮细胞吸收,效率为接种物的 5% 至 6%。当与双细胞 Transwell 单层(上皮细胞和内皮细胞)一起孵育时,结核分枝杆菌以效率(3% 至 4%)转移到下室中。当结核分枝杆菌在单核细胞内时,也能够有效地跨过双细胞紫层。当 A549 肺泡细胞被结核分枝杆菌感染时,受感染的单核细胞穿过屏障的效率比 A549 细胞未感染时更高。我们确定了结核分枝杆菌进入更深组织的两种潜在机制,即穿过上皮细胞易位和进入单核细胞内的血管。
The mechanism(s) by which Mycobacterium tuberculosis crosses the alveolar wall to establish infection in the lung is not well known. In an attempt to better understand the mechanism of translocation and create a model to study the different stages of bacterial crossing through the alveolar wall, we established a two-layer transwell system. M. tuberculosis H37Rv was evaluated regarding the ability to cross and disrupt the membrane. M. tuberculosis invaded A549 type II alveolar cells with an efficiency of 2 to 3% of the initial inoculum, although it was not efficient in invading endothelial cells. However, bacteria that invaded A549 cells were subsequently able to be taken up by endothelial cells with an efficiency of 5 to 6% of the inoculum. When incubated with a bicellular transwell monolayer (epithelial and endothelial cells), M. tuberculosis translocated into the lower chamber with efficiency (3 to 4%). M. tuberculosis was also able to efficiently translocate across the bicellular laver when inside monocytes. Infected monocytes crossed the barrier with greater efficiency, when A549 alveolar cells were infected with M. tuberculosis than when A549 cells were not infected. We identified two potential mechanisms by which M. tuberculosis gains access to deeper tissues, by translocating across epithelial cells and by traveling into the blood vessels within monocytes.