TLR4, NOD1 and NOD2 mediate immune recognition of putative newly identified periodontal pathogens.
TLR4, NOD1 and NOD2 mediate immune recognition of putative newly identified periodontal pathogens.
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DOI：
10.1111/omi.12116
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发表时间：
2016-06
影响因子：
3.7
通讯作者：
Giannobile WV
中科院分区：
文献类型：
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作者：
Marchesan J;Jiao Y;Schaff RA;Hao J;Morelli T;Kinney JS;Gerow E;Sheridan R;Rodrigues V;Paster BJ;Inohara N;Giannobile WV
牙周炎是一种由口腔微生物群与宿主免疫相互作用引起的多菌性炎症性疾病。虽然先天免疫应答对于疾病的发生和发展是重要的，但是识别引起免疫应答的经典和假定的牙周病原体的先天免疫受体尚未阐明。通过使用人类口腔微生物鉴定微阵列（HOMIM），我们确定了多种主要的口腔细菌物种在人类菌斑生物膜，强烈相关的严重牙周炎。对10种已鉴定的菌种进行了更深入的评价，其中6种为经典病原体，4种为推定的新型病原体。使用来自野生型（WT）和toll样受体（TLR）特异性和MyD88敲除（科斯）的人外周血单核细胞（HPBM）和鼠骨髓源性巨噬细胞（BMDM），我们证明了热灭活的密集弯曲杆菌、直弯曲杆菌、感染性月单胞菌、牙髓卟啉单胞菌、牙龈卟啉单胞菌和嗜热唐纳氏菌介导高免疫刺激活性。C. concisus、C. rectus和S. infringe显示出强的TLR4刺激活性。使用来自WT和NOD 1特异性科斯的间皮细胞和表达NOD 2的人胚肾（HEK）细胞的研究表明，隐真杆菌、结节真杆菌和非丝状因子表现出稳健的NOD 1刺激活性，并且牙髓卟啉单胞菌和微小单胞菌具有最高的NOD 2刺激活性。这些研究使我们能够为牙周病发病机制中新鉴定的推定病原体提供重要证据，表明这些细菌通过TLR4，NOD1和NOD2表现出不同的免疫刺激活性（Clinicaltrials.gov NCT01154855）。
Periodontitis is a polymicrobial inflammatory disease that results from the interaction between the oral microbiota and the host immunity. While the innate immune response is important for disease initiation and progression, the innate immune receptors that recognize both classical and putative periodontal pathogens that elicit an immune response have not been elucidated. By using the Human Oral Microbe Identification Microarray (HOMIM), we identified multiple predominant oral bacterial species in human plaque biofilm that strongly associate with severe periodontitis. Ten of the identified species were evaluated in greater depth, 6 being classical pathogens and 4 putative novel pathogens. Using human peripheral blood monocytes (HPBM) and murine bone marrow–derived macrophages (BMDM) from wild-type (WT) and toll-like receptor (TLR)-specific and MyD88 knockouts (KOs), we demonstrated that heat-killed Campylobacter concisus, Campylobacter rectus, Selenomonas infelix, Porphyromonas endodontalis, Porphyromonas gingivalis, and Tannerella forsythia mediate high immunostimulatory activity. C. concisus, C. rectus, and S. infelix exhibited robust TLR4 stimulatory activity. Studies using mesothelial cells from WT and NOD1-specific KOs and NOD2-expressing human embryonic kidney (HEK) cells demonstrated that Eubacterium saphenum, Eubacterium nodatum and Filifactor alocis exhibit robust NOD1 stimulatory activity, and that Porphyromonas endodontalis and Parvimonas micra have the highest NOD2-stimulatory activity. These studies allowed us to provide important evidence on newly-identified putative pathogens in periodontal disease pathogenesis showing that these bacteria exhibit different immunostimulatory activity via TLR4, NOD1, and NOD2 (Clinicaltrials.gov NCT01154855).