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2'-5'-Oligoadenylate synthetase-like protein inhibits intracellular M. tuberculosis replication and promotes proinflammatory cytokine secretion.
Molecular Immunology ( IF 3.2 ) Pub Date : 2019-12-16 , DOI: 10.1016/j.molimm.2019.12.004
G Leisching 1 , A Ali 2 , V Cole 1 , B Baker 1
Affiliation  

Host cytoplasmic surveillance pathways are known to elicit type I interferon (IFN) responses which are crucial to antimicrobial defense mechanisms. Oligoadenylate synthetase-like (OASL) protein has been extensively characterized as a part of the anti-viral mechanism, however a number of transcriptomic studies reveal its upregulation in response to infection with a wide variety of intracellular bacterial pathogens. To date, there is no evidence documenting the role (if any) of OASL during mycobacterium tuberculosis infection. Using two pathogenic strains differing in virulence only, as well as the non-pathogenic M. bovis BCG strain, we observed that pathogenicity and virulence strongly induced OASL expression after 24 h of infection. Further, we observed that OASL knock down led to a significant increase in M. tb CFU counts 96 h post-infection in comparison to the respective controls. Luminex revealed that OASL silencing significantly decreased IL-1β, TNF-α and MCP-1 secretion in THP-1 cells and had no effect on IL-10 secretion. We therefore postulate that OASL regulates pro-inflammatory mediators such as cytokines and chemokines which suppress intracellular mycobacterial growth and survival.

中文翻译:

2'-5'-寡腺苷酸合成酶样蛋白抑制细胞内结核分枝杆菌的复制并促进促炎细胞因子的分泌。

已知宿主细胞质监视途径会引发I型干扰素(IFN)反应,这对抗菌防御机制至关重要。寡腺苷酸合成酶样(OASL)蛋白已被广泛表征为抗病毒机制的一部分,但是许多转录组学研究表明,它响应多种细胞内细菌病原体的感染而被上调。迄今为止,尚无证据证明OASL在结核分枝杆菌感染中的作用(如果有的话)。使用仅在毒力上不同的两个致病菌株以及非致病性牛分枝杆菌BCG菌株,我们观察到,感染24小时后,致病性和毒力强烈诱导了OASL表达。此外,我们观察到OASL的降低导致M的显着增加。与相应对照相比,tb CFU在感染后96小时计数。Luminex发现,OASL沉默可显着降低THP-1细胞中IL-1β,TNF-α和MCP-1的分泌,而对IL-10的分泌没有影响。因此,我们假设OASL调节促炎性介质,例如抑制细胞内分枝杆菌生长和存活的细胞因子和趋化因子。
更新日期:2019-12-27
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