The C-terminal region of the major outer sheath protein of Treponema denticola inhibits neutrophil chemotaxis.
The C-terminal region of the major outer sheath protein of Treponema denticola inhibits neutrophil chemotaxis.
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DOI：
10.1111/omi.12180
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发表时间：
2017-10
影响因子：
3.7
通讯作者：
Visser MB
中科院分区：
文献类型：
--
作者：
Jones MM;Vanyo ST;Visser MB
齿垢密螺旋体是一种口腔螺旋体，与严重的牙周病密切相关。一个突出的毒力因子，主要的外鞘蛋白（Msp），通过改变细胞磷酸肌醇平衡，导致损害的下游趋化性事件，包括肌动蛋白重排，Rac 1激活和Akt激活，响应于化学引诱物刺激的中性粒细胞趋化性。Msp负责与中性粒细胞相互作用的特定区域仍然未知。在这项研究中，我们研究了截短的Msp区域对中性粒细胞趋化性和相关信号通路的抑制作用。用重组蛋白截短物处理小鼠中性粒细胞，然后评估趋化性和相关信号通路活化。趋化性测定表明C-末端区域内的序列，特别是前130个氨基酸，对中性粒细胞趋化性具有最强的抑制作用。与C-末端区域蛋白孵育的中性粒细胞也表现出对Rac 1活化的最大抑制，增加磷酸肌醇磷酸酶活性，并降低Akt活化;协调趋化性受损。此外，孵育与抗体特异性的C-末端区域阻断Msp诱导的抑制趋化性和变性的蛋白质恢复Rac 1激活。与菌株35405相比，来自菌株OTK的Msp在整个多肽中具有许多氨基酸取代，包括C-末端区域，显示出增强的损害中性粒细胞趋化性的能力。总的来说，这些结果表明Msp的C-末端区域是调节中性粒细胞趋化性信号传导的最有效区域，并且可能需要特定的序列和结构。螺旋体如何抑制中性粒细胞反应的知识是有限的，Msp可能是牙周病的一个新的治疗靶点。
Treponema denticola is an oral spirochete strongly associated with severe periodontal disease. A prominent virulence factor, the major outer sheath protein (Msp), disorients neutrophil chemotaxis by altering the cellular phosphoinositide balance, leading to impairment of downstream chemotactic events including actin rearrangement, Rac1 activation and Akt activation in response to chemoattractant stimulation. The specific regions of Msp responsible for interactions with neutrophils remain unknown. In this study, we investigated the inhibitory effect of truncated Msp regions on neutrophil chemotaxis and associated signaling pathways. Murine neutrophils were treated with recombinant protein truncations followed by assessment of chemotaxis and associated signal pathway activation. Chemotaxis assays indicate sequences within the C-terminal region; particularly the first 130 amino acids, have the strongest inhibitory effect on neutrophil chemotaxis. Neutrophils incubated with the C-terminal region protein also demonstrated the greatest inhibition of Rac1 activation, increased phosphoinositide phosphatase activity, and decreased Akt activation; orchestrating impairment of chemotaxis. Furthermore, incubation with antibodies specific to only the C-terminal region blocked the Msp induced inhibition of chemotaxis and denaturing the protein restored Rac1 activation. Msp from the strain OTK, with numerous amino acid substitutions throughout the polypeptide, including the C-terminal region compared to strain 35405, showed increased ability to impair neutrophil chemotaxis. Collectively, these results indicate the C-terminal region of Msp is the most potent region to modulate neutrophil chemotactic signaling and that specific sequences and structure is likely required. Knowledge of how spirochetes dampen neutrophil response is limited and Msp may represent a novel therapeutic target for periodontal disease.
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影响因子：
3.1
作者：
Caimano, MJ;Bourell, KW;Radolf, JD
通讯作者：
Radolf, JD
影响因子：
6.7
作者：
Ding, Y;Haapasalo, M;Sorsa, T
通讯作者：
Sorsa, T
影响因子：
3.2
作者：
Fenno, JC;Wong, GWK;McBride, BC
通讯作者：
McBride, BC
影响因子：
4.3
作者：
Eke PI;Dye BA;Wei L;Slade GD;Thornton-Evans GO;Borgnakke WS;Taylor GW;Page RC;Beck JD;Genco RJ
通讯作者：
Genco RJ
影响因子：
3.5
作者：
CHENG, SL;CHAN, ECS
通讯作者：
CHAN, ECS