中文摘要：NLRP3炎性体能够诱导机体产生IL-1和IL18，在抗微生物病原的宿主防御系统中起到重要作用。唾液支原体和肺炎支原体细胞能够激活小鼠骨髓源性巨噬细胞（BMMs），诱导产生IL-1和IL-18。这两种支原体诱导TLR2缺陷小鼠骨髓源性巨噬细胞（BMMs）产生IL-1的活性弱于诱导C57BL/6小鼠骨髓源性巨噬细胞（B6BMMs），这一过程可能与不同支原体的脂蛋白相关。唾液支原体和肺炎支原体脂蛋白（MsLP 和 MpLP）、源于唾液支原体的脂肽FSL-1能够诱导C57BL/6小鼠骨髓源性巨噬细胞（B6BMMs）产生IL-1，对caspase-1-、NLRP3- 或ASC缺陷型小鼠骨髓源性巨噬细胞不产生作用。蛋白酶K处理不会下调MsLP 和 MpLP的活性，这表明活性位点为N-末端的脂肽结构。培养30分钟后，B6BMMs融合支原体N末端脂肽FSL-1，FSL-1包含的核内体在2小时左右开始与溶酶体融合，然后FSL-1从LAMP-1(+)核内体转向细胞溶质中。在B6BMMs细胞溶质中人工导入FSL-1能够显著增强诱导IL-1产生的活性。FSL-1及代表性NLRP3炎性体活化剂尼日利亚霉素能够诱导产生NLRP3/ASC微粒，但FSL-1与NLRP3/ASC微粒的位置不同。
 
外文摘要：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-1 (IL-1) and IL-18. Mycoplasma salivarium and Mycoplasma pneumoniae cells activated murine bone marrow-derived macrophages (BMMs) to induce production of IL-1, IL-1, and IL-18. The IL-1 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-1 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 30min after incubation, FSL-1-containing endosomes started to fuse with the lysosomes around 2hours, 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-1 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.
外文关键词：FSL-1； interleukin-1； Mycoplasma pneumoniae； Mycoplasma salivarium； mycoplasmal lipoproteins； nucleotide-binding oligomerization domain-like receptor family； pyrin domain containing 3
作者：Saeki, A； Sugiyama, M； Hasebe, A； Suzuki, T； Shibata, K
作者单位：日本北海道大学
期刊名称：MOLECULAR ORAL MICROBIOLOGY
期刊影响因子：2.853
出版年份：2018
出版刊次：7
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