期刊
MICROBIOLOGY AND IMMUNOLOGY
卷 64, 期 4, 页码 270-279出版社
WILEY
DOI: 10.1111/1348-0421.12770
关键词
Anaplasma phagocytophilum; endoplasmic reticulum stress; inositol-requiring enzyme-1; intracellular proliferation; X-Box-binding protein 1
资金
- Japan Agency for Medical Research and Development [JP17fk0108310]
- Ministry of Health, Labour and Welfare [H21-ShinkouIppan-006, H24-Shinkou-Ippan-008]
- Japan Society for the Promotion of Science [23590514, 26460532]
- Grants-in-Aid for Scientific Research [23590514] Funding Source: KAKEN
Anaplasma phagocytophilum, an obligate intracellular bacterium that propagates within host granulocytes, is considered to modify the host intracellular environment for pathogenesis. However, the mechanism(s) underlying such host modifications remain unclear. Here, we aimed to investigate the relation between A. phagocytophilum and endoplasmic reticulum (ER) stress in THP-1 cells. A. phagocytophilum activated the three ER stress sensors: inositol-requiring enzyme-1 (IRE1), protein kinase RNA-like endoplasmic reticulum kinase (PERK), and activating transcription factor-6 (ATF6). IRE1 activation occurred immediately after host cell invasion by A. phagocytophilum; however, the activated IRE1-induced splicing of X-box-binding protein 1 was not promoted during A. phagocytophilum infection. This suppression was sustained even after the doxycycline-mediated elimination of intracellular A. phagocytophilum. IRE1 knockdown accelerated A. phagocytophilum-induced apoptosis and decreased intracellular A. phagocytophilum. These data suggest that A. phagocytophilum utilizes IRE1 activation to promote its own intracellular proliferation. Moreover, PERK and ATF6 partially mediated A. phagocytophilum-induced apoptosis by promoting the expression of CCAAT/enhancer-binding protein homologous protein, which induces the transcription of several proapoptotic genes. Thus, A. phagocytophilum possibly manipulates the host ER stress signals to facilitate intracellular proliferation and infection of surrounding cells before/after host cell apoptosis.
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