Porphyromonas gingivalis induces penetration of lipopolysaccharide and peptidoglycan through the gingival epithelium via degradation of coxsackievirus and adenovirus receptor
Porphyromonas gingivalis induces penetration of lipopolysaccharide and peptidoglycan through the gingival epithelium via degradation of coxsackievirus and adenovirus receptor
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DOI：
10.1111/cmi.13388
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发表时间：
2021-09-07
影响因子：
3.4
通讯作者：
Amano, Atsuo
中科院分区：
文献类型：
--
作者：
Takeuchi, Hiroki;Yamaga, Shunsuke;Amano, Atsuo
牙龈卟啉单胞菌是人类牙周炎的主要病原体，其在牙龈上皮表面的天然免疫失调。我们以前报道，细菌特异性降解连接粘附分子1（JAM 1），导致牙龈上皮屏障破坏。然而，其他JAM家族蛋白在由牙龈卟啉单胞菌引起的上皮屏障失调中的功能尚未完全了解。目前的结果表明，牙龈卟啉菌蛋白酶，精氨酸特异性或赖氨酸特异性半胱氨酸蛋白酶产生的牙龈卟啉菌，特异性降解柯萨奇病毒和腺病毒受体（CXADR），一个JAM家族蛋白，在R145和K235牙龈上皮细胞。相反，发现牙龈卟啉菌蛋白酶缺陷型牙龈卟啉单胞菌菌株在CXADR降解方面受损。此外，在人工牙龈上皮中敲低CXADR增加了对右旋糖酐40 kDa、脂多糖和肽聚糖的渗透性，而在牙龈上皮组织模型中CXADR的过表达阻止了牙龈卟啉单胞菌感染后这些药物的渗透。总之，这些结果表明牙龈卟啉单胞菌牙龈卟啉菌蛋白酶通过降解CXADR以及JAM 1破坏复层鳞状上皮屏障，这允许细菌毒力因子有效转移到上皮下组织中。摘要牙龈卟啉单胞菌是一种牙周病原体，可降解牙龈上皮组织中的柯萨奇病毒和腺病毒受体（CXADR），这是一种JAM家族蛋白。牙龈卟啉单胞菌牙龈卟啉菌蛋白酶，半胱氨酸蛋白酶，在R145和K235降解CXADR。牙龈卟啉单胞菌降解CXADR导致脂多糖和肽聚糖通过牙龈上皮组织的渗透性增加。
Porphyromonas gingivalis is a major pathogen of human periodontitis and dysregulates innate immunity at the gingival epithelial surface. We previously reported that the bacterium specifically degrades junctional adhesion molecule 1 (JAM1), causing gingival epithelial barrier breakdown. However, the functions of other JAM family protein(s) in epithelial barrier dysregulation caused by P. gingivalis are not fully understood. The present results show that gingipains, Arg-specific or Lys-specific cysteine proteases produced by P. gingivalis, specifically degrade coxsackievirus and adenovirus receptor (CXADR), a JAM family protein, at R145 and K235 in gingival epithelial cells. In contrast, a gingipain-deficient P. gingivalis strain was found to be impaired in regard to degradation of CXADR. Furthermore, knockdown of CXADR in artificial gingival epithelium increased permeability to dextran 40 kDa, lipopolysaccharide and peptidoglycan, whereas overexpression of CXADR in a gingival epithelial tissue model prevented penetration by those agents following P. gingivalis infection. Together, these results suggest that P. gingivalis gingipains breach the stratified squamous epithelium barrier by degrading CXADR as well as JAM1, which allows for efficient transfer of bacterial virulence factors into subepithelial tissues. Takeaways P. gingivalis, a periodontal pathogen, degraded coxsackievirus and adenovirus receptor (CXADR), a JAM family protein, in gingival epithelial tissues. P. gingivalis gingipains, cysteine proteases, degraded CXADR at R145 and K235. CXADR degradation by P. gingivalis caused increased permeability to lipopolysaccharide and peptidoglycan through gingival epithelial tissues.