Immune response of macrophages induced by Porphyromonas gingivalis requires HmuY protein
Immune response of macrophages induced by Porphyromonas gingivalis requires HmuY protein
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DOI：
10.1016/j.imbio.2016.07.007
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发表时间：
2016-12-01
期刊：
影响因子：
2.8
通讯作者：
Olczak, Teresa
中科院分区：
文献类型：
--
作者：
Gmiterek, Anna;Klopot, Anna;Olczak, Teresa
牙龈卟啉单胞菌是引起慢性牙周炎的主要病原菌，也是引起慢性牙周炎的主要致病菌。我们使用基于细胞的感染模型研究了牙龈卟啉单胞菌，特别是HmuY蛋白，在参与Toll样受体（TLR）诱导的信号传导途径的基因表达中的作用。PMA处理后分化为巨噬细胞的U937和THP-1细胞对牙龈卟啉单胞菌引起的感染的基因表达模式略有不同，主要是编码NF-κ B B、TLR 7、TLR 2、TLR 8、促炎细胞因子的基因表达增加（IL-1 β、IL-6、TNF α）、抗炎细胞因子（IL-10）和化学模型（CCL 3L 1、CCL 4、CXCL 10、CXCL 11、PTX 3）。缺乏功能性hmuY基因的牙龈卟啉单胞菌刺激巨噬细胞的免疫应答，尽管与野生型菌株相比以不同的方式，主要是通过编码NF-κ B、IL-1 β、IL-10、CD 80、PTX 3和CCL 31 L的基因的较低表达。单独的纯化的HmuY蛋白诱导编码IL-6、IL-10、TNF α、CCL 3L 1和CCL 4的基因的表达。我们得出结论，巨噬细胞主要通过TLR 7诱导的途径对牙龈卟啉单胞菌感染作出反应。此外，牙龈卟啉单胞菌HmuY是重要的毒力因子之一，它能使牙龈卟啉单胞菌在血红素限制的宿主环境中体内生长，导致巨噬细胞产生有效的免疫应答。(C)2016 Elsevier GmbH. All rights reserved.
The main etiologic agent and a key pathogen responsible for initiation and progression of chronic periodontitis is Porphyromonas gingivalis. We examined the role of P. gingivalis, with particular interest to HmuY protein, in expression of genes involved in Toll-like receptor (TLR)-induced signaling pathways using cell-based infection model. U937 and THP-1 cells differentiated toward macrophages by PMA treatment responded to P. gingivalis-caused infection in slightly different gene expression pattern, mainly by higher expression of genes encoding NF-kappa B, TLR7, TLR2, TLR8, pro-inflammatory cytokines (IL-1 beta, IL-6, TNF alpha), anti-inflammatory cytokine (IL-10), and chemoldnes (CCL3L1, CCL4, CXCL10, CXCL11, PTX3). P. gingivalis lacking functional hmuY gene stimulates immune response of macrophages, albeit in a different manner as compared with the wild-type strain, mainly by lower expression of genes encoding NF-kappa B, IL-1 beta, IL-10, CD80, PTX3, and CCL31L, The purified HmuY protein alone induced expression of genes encoding IL-6, IL-10, TNF alpha, CCL3L1, and CCL4. We conclude that macrophages respond to P. gingivalis infection mostly by TLR7-induced pathway(s). Moreover, P. gingivalis HmuY is one of important virulence factors, which allows P. gingivalis for in vivo growth in the heme-limited host environment, resulting in efficient immune response of macrophages. (C) 2016 Elsevier GmbH. All rights reserved.