Department of Surgery, University of Otago Christchurch, Christchurch, New Zealand.
Infect Immun. 2012 Nov;80(11):3768-75. doi: 10.1128/IAI.00534-12. Epub 2012 Aug 13.
Mycobacterium avium subsp. paratuberculosis is a bacterium sometimes found in human blood and tissue samples that may have a role in the etiology of Crohn's disease in humans. To date, however, there have been few studies examining the interactions of these bacteria with human cells. Using the THP-1 human monocytic cell line, this study shows that the uptake and trafficking of M. avium subsp. paratuberculosis in human cells are cholesterol dependent and that these bacteria localize to cholesterol-rich compartments that are slow to acidify. M. avium subsp. paratuberculosis bacteria containing phagosomes stain for the late endosomal marker Rab7, but recruitment of the Rab7-interacting lysosomal protein that regulates the fusion of bacterium-containing phagosomes with lysosomal compartments and facilitates subsequent bacterial clearance is significantly reduced. Disruption of phagosome acidification via this mechanism may contribute to M. avium subsp. paratuberculosis persistence in human cells, but there was no evidence that internalized M. avium subsp. paratuberculosis also affects the survival of bacteria taken up during a secondary phagocytic event.
分支杆菌偶发亚种是一种有时存在于人类血液和组织样本中的细菌,它可能在人类克罗恩病的病因中起作用。然而,迄今为止,很少有研究检查这些细菌与人细胞的相互作用。本研究使用 THP-1 人单核细胞系表明,分支杆菌偶发亚种在人细胞中的摄取和运输依赖于胆固醇,并且这些细菌定位于酸化缓慢的富含胆固醇的隔室中。含有吞噬体的分支杆菌偶发亚种 Rab7 标记晚期内体,但调节含有细菌的吞噬体与溶酶体隔室融合并促进随后细菌清除的 Rab7 相互作用的溶酶体蛋白的募集显著减少。通过这种机制破坏吞噬体酸化可能有助于分支杆菌偶发亚种在人细胞中的持续存在,但没有证据表明内化的分支杆菌偶发亚种也会影响二次吞噬事件中摄取的细菌的存活。