Bahnan Wael, Boettner Douglas R, Westermark Linda, Fällman Maria, Schesser Kurt
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
PLoS One. 2015 Aug 14;10(8):e0133298. doi: 10.1371/journal.pone.0133298. eCollection 2015.
Microbial pathogens and host immune cells each initiate events following their interaction in an attempt to drive the outcome to their respective advantage. Here we show that the bacterial pathogen Yersinia pseudotuberculosis sustains itself on the surface of a macrophage by forming acidic fluid-accessible compartments that are partially bounded by the host cell plasma membrane. These Yersinia-containing acidic compartments (YACs) are bereft of the early endosomal marker EEA1 and the lysosomal antigen LAMP1 and readily form on primary macrophages as well as macrophage-like cell lines. YAC formation requires the presence of the Yersinia virulence plasmid which encodes a type III secretion system. Unexpectedly, we found that the initial formation of YACs did not require translocation of the type III effectors into the host cell cytosol; however, the duration of YACs was markedly greater in infections using translocation-competent Y. pseudotuberculosis strains as well as strains expressing the effector YopJ. Furthermore, it was in this translocation- and YopJ-dependent phase of infection that the acidic environment was critical for Y. pseudotuberculosis survival during its interaction with macrophages. Our findings indicate that during its extracellular phase of infection Y. pseudotuberculosis initiates and then, by a separate mechanism, stabilizes the formation of a highly intricate structure on the surface of the macrophage that is disengaged from the endocytic pathway.
微生物病原体和宿主免疫细胞在相互作用后都会引发一系列事件,试图使结果朝着各自有利的方向发展。在此,我们表明,细菌病原体假结核耶尔森菌通过形成部分由宿主细胞质膜界定的酸性液体可及区室,在巨噬细胞表面维持自身存活。这些含有耶尔森菌的酸性区室(YACs)缺乏早期内体标记物EEA1和溶酶体抗原LAMP1,并且在原代巨噬细胞以及巨噬细胞样细胞系中很容易形成。YAC的形成需要耶尔森菌毒力质粒的存在,该质粒编码III型分泌系统。出乎意料的是,我们发现YAC的最初形成并不需要III型效应子转运到宿主细胞胞质溶胶中;然而,在使用具有转运能力的假结核耶尔森菌菌株以及表达效应子YopJ的菌株进行感染时,YAC的持续时间明显更长。此外,正是在这种依赖转运和YopJ的感染阶段,酸性环境对于假结核耶尔森菌与巨噬细胞相互作用期间的存活至关重要。我们的研究结果表明,在其细胞外感染阶段,假结核耶尔森菌启动并随后通过一种独立的机制,稳定在巨噬细胞表面形成一种与内吞途径分离的高度复杂结构。