Department of Microbiology and Immunology, Seoul National University College of Medicine, Jongno-Gu, Seoul, Republic of Korea.
Infect Immun. 2013 Feb;81(2):552-9. doi: 10.1128/IAI.00861-12. Epub 2012 Dec 10.
Orientia tsutsugamushi, the causative agent of scrub typhus, is an obligate intracellular pathogen. After entry into host cells, the bacterium rapidly escapes from the endosomal pathway and replicates in the cytosol of eukaryotic host cells. Here we show that O. tsutsugamushi infection efficiently promotes cellular autophagy, a cell-autonomous defense mechanism of innate immunity. However, most of the internalized bacteria barely colocalized with the induced autophagosomes, even when stimulated with rapamycin, a chemical inducer of autophagy. Treatment of infected cells with tetracycline suppressed bacterial evasion from autophagy and facilitated O. tsutsugamushi targeting to autophagosomes, suggesting that the intracellular pathogen may be equipped with a bacterial factor or factors that block autophagic recognition. Finally, we also found that chemical modulators of cellular autophagy or genetic knockout of the atg3 gene does not significantly affect the intracellular growth of O. tsutsugamushi in vitro. These results suggest that O. tsutsugamushi has evolved to block autophagic microbicidal defense by evading autophagic recognition even though it activates the autophagy pathway during the early phase of infection.
恙虫病东方体是恙虫病的病原体，是一种必需的细胞内病原体。进入宿主细胞后，细菌迅速从内体途径逃逸，并在真核宿主细胞的细胞质中复制。在这里，我们表明恙虫病东方体感染有效地促进了细胞自噬，这是先天免疫的一种细胞自主防御机制。然而，即使在用雷帕霉素（一种自噬的化学诱导剂）刺激时，大多数内化的细菌几乎没有与诱导的自噬体共定位，甚至在用四环素处理感染细胞时，细菌也能逃避自噬作用，并促进恙虫病东方体靶向自噬体，这表明这种细胞内病原体可能具有阻止自噬识别的细菌因子或因子。最后，我们还发现细胞自噬的化学调节剂或 atg3 基因的遗传敲除并不显著影响恙虫病东方体在体外的体内生长。这些结果表明，尽管恙虫病东方体在感染早期激活了自噬途径，但它通过逃避自噬识别，进化出了阻止自噬杀菌防御的能力。
