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Activation of NLRP3 inflammasome in macrophages by mycoplasmal lipoproteins and lipopeptides.
Molecular Oral Microbiology ( IF 3.7 ) Pub Date : 2018-05-29 , DOI: 10.1111/omi.12225
A Saeki 1 , M Sugiyama 1 , A Hasebe 1 , T Suzuki 2 , K Shibata 1
Affiliation  

The NLRP3 inflammasome, an intracellular sensor consisting of the nucleotide‐binding oligomerization domain‐like receptor family, pyrin domain containing 3 (NLRP3), the adaptor protein apoptosis‐associated speck‐like protein containing a caspase‐recruitment domain (ASC), and procaspase‐1, plays critical roles in host defense against microbial pathogens by inducing production of interleukin‐1β (IL‐1β) and IL‐18. Mycoplasma salivarium and Mycoplasma pneumoniae cells activated murine bone marrow‐derived macrophages (BMMs) to induce production of IL‐1α, IL‐1β, and IL‐18. The IL‐1β production‐inducing activities of these mycoplasmas toward BMMs from Toll‐like receptor 2 (TLR2)‐deficient mice were significantly attenuated compared with those from C57BL/6 mice (B6BMMs). This result suggests the possibility that their lipoproteins as TLR2 agonists are involved in the activity. Lipoproteins of M. salivarium and M. pneumoniae (MsLP and MpLP), and the M. salivarium‐derived lipopeptide FSL‐1 induced IL‐1β production by B6BMMs, but not by BMMs from caspase‐1‐, NLRP3‐ or ASC‐deficient mice. The activities of MsLP and MpLP were not downregulated by the proteinase K treatment, suggesting that the active sites are their N‐terminal lipopeptide moieties. B6BMMs internalized the mycoplasmal N‐terminal lipopeptide FSL‐1 at least 30 min after incubation, FSL‐1‐containing endosomes started to fuse with the lysosomes around 2 hours, and then FSL‐1 translocated into the cytosol from LAMP‐1+ endosomes. The artificial delivery of FSL‐1 into the cytosol of B6BMMs drastically enhanced the IL‐1β production‐inducing activity. FSL‐1 as well as the representative NLRP3 inflammasome activator nigericin induced the NLRP3/ASC speck, but FSL‐1 located in a compartment different from the NLRP3/ASC speck.

中文翻译:

支原体脂蛋白和脂肽激活巨噬细胞中的NLRP3炎性体。

NLRP3炎症小体,一种细胞内传感器,由核苷酸结合的寡聚化结构域样受体家族,含3的吡喃结构域(NLRP3),包含胱天蛋白酶募集结构域(ASC)的衔接蛋白凋亡相关斑点样蛋白和蛋白酶‐1通过诱导白介素-1β(IL-1β)和IL-18的产生在抵抗微生物病原体的宿主防御中起关键作用。唾液支原体肺炎支原体细胞激活鼠骨髓源性巨噬细胞(BMM),以诱导IL-1α,IL-1β和IL-18的产生。与C57BL / 6小鼠(B6BMM)相比,Toll样受体2(TLR2)缺陷小鼠对这些支原体的IL-1β产生诱导活性显着减弱。该结果表明其脂蛋白作为TLR2激动剂参与该活性的可能性。唾液支原体肺炎支原体的脂蛋白(MsLP和MpLP)以及唾液支原体衍生的脂肽FSL-1诱导B6BMM产生IL-1β,但不引起caspase-1,NLRP3或ASC缺陷小鼠的BMM产生。蛋白酶K处理并没有下调MsLP和MpLP的活性,这表明活性位点是它们的N末端脂肽部分。B6BMMs在孵育至少30分钟后将支原体N末端脂肽FSL-1内在化,含FSL-1的内体在大约2小时后开始与溶酶体融合,然后FSL-1从LAMP-1 +转移入细胞质内体。将FSL-1人工输送到B6BMM的细胞质中可大大增强IL-1β的生产诱导活性。FSL-1和代表性的NLRP3炎性小体激活剂尼日利亚霉素诱导了NLRP3 / ASC斑点,但FSL-1处于与NLRP3 / ASC斑点不同的隔室中。
更新日期:2018-05-29
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