Article
Multidisciplinary Sciences
Xiaoyang Ma, Yoon-Jung Shin, Jong-Wook Yoo, Hee-Seo Park, Dong-Hyun Kim
Summary: The study found a close connection between periodontitis caused by Porphyromonas gingivalis (PG) infection and Alzheimer's disease. PG-derived extracellular vesicles (pEVs) containing inflammation-inducing factors may lead to memory impairment and cognitive decline. Both PG and pEVs can enter the brain through the periodontal blood pathways and trigeminal nerve, causing cognitive decline and potentially resulting in colitis and gut dysbiosis.
JOURNAL OF ADVANCED RESEARCH
(2023)
Article
Multidisciplinary Sciences
Liping Wang, Dongliang Liang, Yinyin Huang, Yunxin Chen, Xiaocong Yang, Zhijun Huang, Yiqin Jiang, Hanfu Su, Lijing Wang, Janak L. Pathak, Linhu Ge
Summary: This study investigates the role of serum amyloid P component (SAP) in oral microbiome modulation and periodontitis pathogenicity. It is found that SAP deficiency aggravates periodontitis possibly due to impaired macrophage phagocytosis of Porphyromonas gingivalis mediated by the C5a-C5aR signaling.
JOURNAL OF ADVANCED RESEARCH
(2023)
Article
Multidisciplinary Sciences
Min Wang, Lili Li, Jun Qian, Nannan Wang, Jun Bao, Jiangyue Lu, Faming Chen, Yanfen Li, Yangheng Zhang, Fuhua Yan
Summary: In this study, the salivary microbiota from patients with periodontitis was transferred to obese mice induced by high-fat diet to investigate the influence on gut microbiome and liver metabolism. The results showed that periodontitis salivary microbiota altered gut microbiota composition and exacerbated intestinal barrier dysfunction, leading to activation of toll-like receptor 4 signaling and release of pro-inflammatory factors in the liver. Moreover, the upregulation of the tryptophan-kynurenine-AhR signal axis in the liver was associated with aggravated hepatic steatosis and dysregulation of glucolipid metabolism during NAFLD development. This study suggests that periodontitis salivary microbiota may worsen the pathological progression of NAFLD in the context of obesity, with the tryptophan-AhR pathway potentially playing a key role.
Article
Immunology
Zihan Li, Qiuxia Huang, Zhuoran Wang, Lijia Huang, Lisha Gu
Summary: Periodontitis is a dysbiosis condition caused by the coordinated action of multiple members within the microbial consortium. This study demonstrates that Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans can alter the structure and composition of subgingival microbiome, leading to dysbiosis and impaired epithelium function. P. gingivalis drives the commensal microbiome towards dysbiosis, while A. actinomycetemcomitans enhances the symbiotic state.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Immunology
Xiaoxiao Hao, Zhaofei Li, Wei Li, Jannet Katz, Suzanne M. Michalek, Scott R. Barnum, Lucas Pozzo-Miller, Takashi Saito, Takaomi C. Saido, Qin Wang, Erik D. Roberson, Ping Zhang
Summary: Periodontitis may worsen the development and severity of Alzheimer's disease (AD), but the mechanism by which it does so remains unclear. Using a mouse model, this study found that oral infection worsened cognitive impairment and accelerated amyloid beta accumulation in AD mice. The study also revealed that periodontal infection complicates the neuroinflammatory status established by AD and amplifies microglial activation, neuroinflammation, and synaptic tagging through brain overactivation of complement C1q.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Gina R. Lewin, Kendall S. Stocke, Richard J. Lamont, Marvin Whiteley
Summary: This study characterizes the behavior and virulence of the periodontal pathogen Porphyromonas gingivalis during human infection. It reveals that P. gingivalis is highly expressed in diseased samples, with genes related to virulence factors and growth/matabolism being actively expressed. The study also shows that the gene expression of P. gingivalis during periodontitis is highly conserved with logarithmic laboratory growth, suggesting that simple test tube growth can be used as a model for studying P. gingivalis biology.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Analytical
Seonhwa Park, Kiryeon Park, Hee Sam Na, Jin Chung, Haesik Yang
Summary: An electrochemical biosensor for sensitive detection of Porphyromonas gingivalis in saliva was developed without the need for washing and separation steps. This biosensor can be used as an initial diagnosis method to distinguish between healthy people and patients with periodontal diseases.
ANALYTICAL CHEMISTRY
(2021)
Article
Biotechnology & Applied Microbiology
Rui Li, Mengjie Hou, Liying Yu, Wen Luo, Jie Kong, Renmei Yu, Ruihan Liu, Qian Li, Lisi Tan, Chunling Pan, Hongyan Wang
Summary: This study aimed to investigate the effects of salivary histatin 5 (Hst5) on Porphyromonas gingivalis (P. gingivalis) biofilms in vitro and in vivo and the possible mechanisms. The results showed that 25μg/mL Hst5 effectively inhibited biofilm formation and increased concentrations of Hst5 increased the inhibitive effect. Hst5 could regulate membrane function and metabolic processes in P. gingivalis, and RpoD and FeoB proteins might play important roles in this process. Moreover, 100μg/mL Hst5 inhibited periodontal inflammation and alveolar bone loss in rat periodontitis through its antibacterial and anti-inflammatory effects.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2023)
Article
Immunology
Banndith Cheat, Coralie Torrens, Asmaa Foda, Brigitte Baroukh, Jeremy Sadoine, Lotfi Slimani, Veronique Witko-Sarsat, Olivier Huck, Marjolaine Gosset, Jerome Bouchet
Summary: Our study investigates the role of NLRP3 in periodontitis, demonstrating its ambiguous role in neutrophils and its interaction with Porphyromonas gingivalis. The study reveals that NLRP3 is involved in regulatory pathways that limit periodontitis in mouse models, but its protective effect is diminished in the presence of P. gingivalis. Overexpression of NLRP3 in connective tissue leads to increased production of mature IL-1 beta and mobilization of neutrophils, while NLRP3 deficiency results in lower IL-1 beta expression and almost no neutrophil mobilization.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Microbiology
Izabela Ciaston, Joanna Budziaszek, Dorota Satala, Barbara Potempa, Andrew Fuchs, Maria Rapala-Kozik, Danuta Mizgalska, Ewelina Dobosz, Richard J. Lamont, Jan Potempa, Joanna Koziel
Summary: The study found that inactive gingipains still elicit a strong inflammatory response in gingival tissues, which may contribute to the progression of periodontitis and bone resorption. Moreover, host molecules were identified as receptors for proteolytically inactivated gingipains. The broad distribution of these receptors in human tissues suggests their involvement in systemic diseases associated with periodontal pathogens.
Article
Immunology
Xiaomiao Fan, Shaowen Zheng, Chen Chen, Li Lin, Hongyan Wang, Yuqin Shen, Yaping Pan, Chen Li
Summary: This study investigated the role of sialidase in immune evasion of P. gingivalis by examining its effects on macrophage polarization, antigen presentation, and phagocytosis. The results showed that Delta PG0352 strain, lacking the sialidase gene, was more easily cleared by macrophages and exhibited increased M1 polarization, antigen presentation, and phagocytosis compared to the wild-type strain. This suggests that sialidase plays an important role in P. gingivalis immune evasion.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Immunology
Shuhui Zhou, Yaoting Ji, Hantao Yao, Haiying Guo, Zichen Zhang, Zijun Wang, Minquan Du
Summary: This study found that ginsenoside Rd has inhibitory effects on periodontitis-related bacteria and inflammatory response, as well as the ability to inhibit bone resorption induced by periodontitis. The results provide potential evidence for the development of Rd as a medication for the control and prevention of periodontitis.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Josefa Nunez-Belmar, Mauricio Morales-Olavarria, Emiliano Vicencio, Rolando Vernal, Juan P. Cardenas, Cristian Cortez
Summary: This review discusses the use of different -omics technologies and techniques in studying the pathogenic potential of P. gingivalis and its interaction with the host.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Dentistry, Oral Surgery & Medicine
Marta Kaminska, Malgorzata Benedyk-Machaczka, Karina Adamowicz, Ardita Aliko, Kamila Drzazga, Klaudia Slysz, Ewa Bielecka, Jan Potempa, Piotr Mydel
Summary: This study evaluated the antimicrobial effects of bestatin, a potential drug candidate for chronic periodontitis (CP). The results showed that bestatin exhibited bacteriostatic activity against periodontopathogens and controlled the formation and composition of the biofilm. Additionally, bestatin promoted the phagocytosis of periodontopathogens by immune cells and reduced inflammation. These findings suggest that bestatin is a promising choice for the treatment and prevention of periodontitis.
JOURNAL OF PERIODONTOLOGY
(2023)
Article
Dentistry, Oral Surgery & Medicine
Sowon Park, Inyoung Kim, Soo Jung Han, Soyeon Kwon, Eun-Ji Min, Wonkyoung Cho, Hong Koh, Bon-Nyeo Koo, Jung Seok Lee, Jae-Sung Kwon, Kyoung Yul Seo, Jong-Won Ha, Young Mi Park
Summary: This study investigated the link between periodontitis and intestinal dysbiosis in relation to atherosclerosis. The findings suggest that oral infection with Porphyromonas gingivalis (PG) can promote atherosclerosis and induce metabolic changes, as well as alter the intestinal microbiota.
JOURNAL OF CLINICAL PERIODONTOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Kridtapat Sirisereephap, Tomoki Maekawa, Hikaru Tamura, Takumi Hiyoshi, Hisanori Domon, Toshihito Isono, Yutaka Terao, Takeyasu Maeda, Koichi Tabeta
Summary: Periodontitis is a common oral disease resulting from dysbiosis of the oral microbiome, leading to interference with the host immune system and bone destruction. Immune cells activate periodontal ligament cells to express RANKL and promote osteoclast activity, with osteocytes playing an active role in periodontitis progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Immunology
Tom E. Mollnes, Benjamin S. Storm, Ole L. Brekke, Per H. Nilsson, John D. Lambris
Summary: The complement system, initially thought to protect the host from infection, has been shown to have numerous other functions and plays a major role in various diseases. Traditional reductionistic models of complement research are limited, and there is a need for holistic models that retain complement activity and allow for the study of interactions with other inflammatory systems. Two such models using anticoagulated whole blood are described here, which will be useful in further understanding complement-driven diseases.
SEMINARS IN IMMUNOLOGY
(2022)
Article
Immunology
Thyago Bispo Leonel, Joel Jose Megale Gabrili, Carla Cristina Squaiella-Baptistao, Trent M. Woodruff, John D. Lambris, Denise V. Tambourgi
Summary: This study analyzed the effects of Bothrops jararaca snake venom on the complement system and innate immunity. The venom was found to activate the complement system and induce inflammatory responses. Inhibition of the complement system may represent a potential therapeutic approach for Bothrops jararaca envenoming.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Critical Care Medicine
Relber A. Goncales, Helder Novais Bastos, Claudio Duarte-Oliveira, Daniela Antunes, Oksana Sokhatska, Maria Jacob, Rui Rolo, Claudia F. Campos, Sergio D. Sasaki, Alessia Donato, Sarah N. Mapelli, Sandra Costa, Conceicao Souto Moura, Luis Delgado, Antonio Morais, Egidio Torrado, Frank L. van de Veerdonk, Thomas Weichhart, John D. Lambris, Ricardo Silvestre, Cecilia Garlanda, Alberto Mantovani, Cristina Cunha, Agostinho Carvalho
Summary: This study reveals the role of long pentraxin PTX3 in sarcoidosis, finding that its deficiency can lead to amplified complement activation and promote granuloma formation. The results suggest that PTX3 plays a pivotal role in macrophages to restrain granulomatous inflammation and this signaling axis holds therapeutic potential for targeting granuloma formation in sarcoidosis.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Editorial Material
Oncology
George Hajishengallis, Triantafyllos Chavakis
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Review
Immunology
Lydia Kalafati, Aikaterini Hatzioannou, George Hajishengallis, Triantafyllos Chavakis
Summary: The principle of trained immunity represents innate immune memory due to sustained, mainly epigenetic, changes triggered by endogenous or exogenous stimuli in bone marrow (BM) progenitors and their innate immune cell progeny. Neutrophils, as the most abundant innate immune cell population, play a crucial role in trained immunity. However, trained immunity may have detrimental outcomes in chronic inflammation.
IMMUNOLOGICAL REVIEWS
(2023)
Review
Immunology
Silvia M. Uriarte, George Hajishengallis
Summary: Neutrophils play a crucial role in periodontal health and disease, but their absence or dysfunction can lead to severe periodontitis at an early age. Both an excess or hyperactive neutrophil response can disrupt the balance of host-microbe interactions in the periodontium, resulting in inflammation and dysbiosis. Periodontal pathogens can further exploit neutrophil responses to their advantage, causing harm to the host.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Immunology
Hui Wang, Hidetaka Ideguchi, Tetsuhiro Kajikawa, Dimitrios C. Mastellos, John D. Lambris, George Hajishengallis
Summary: The complement and Th17 cells play crucial roles in periodontitis. Complement activation generates critical cytokines, including IL-6 and IL-23, which are necessary for the expansion of Th17 cells. Additionally, IL-6 is important for inflammation and bone loss in periodontitis.
JOURNAL OF IMMUNOLOGY
(2022)
Review
Hematology
Christina Lamers, Daniel Ricklin, John D. Lambris
Summary: The number of complement inhibitors approved for therapeutic use or in late-stage clinical trials has expanded rapidly in recent years. The sudden emergence of this area in biotech start-ups and pharmaceutical companies is surprising considering the well-established involvement of the complement system in various clinical conditions. However, the complement system has unique characteristics that have delayed its recognition as a traditional drug target, such as concerns about safety and the complexity of its involvement in biological processes.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Review
Microbiology
George Hajishengallis, Richard J. Lamont, Hyun Koo
Summary: Oral microbial communities form complex spatial structures and regulate their collective function and adaptability through sophisticated physical and chemical signaling systems. The balance or dysbiosis of these communities, influenced by intra-community interactions, host and environmental factors, plays a crucial role in oral diseases such as periodontitis and dental caries. Dysbiosis in oral polymicrobial communities also has systemic effects, partly due to the colonization of oral pathogens in extra-oral tissues.
CELL HOST & MICROBE
(2023)
Article
Cell Biology
Amelie Kuhn, Jana Riegger, Graciosa Q. Teixeira, Markus Huber-Lang, John D. Lambris, Cornelia Neidlinger-Wilke, Rolf E. Brenner
Summary: Terminal complement complex deposition was found in human degenerated discs. The study investigated the mechanisms and effects of terminal complement activation in annulus fibrosus (AF) cells. Complement inhibitors effectively suppressed anaphylatoxin generation and TCC deposition induced by zymosan. Gene expression of ADAMTS4, MMP1, and COX2 was influenced by C3 and C5 blockade. Degenerated endplate tissue secreted soluble factors that enhanced direct C5 cleavage. These findings suggest the functional involvement of terminal complement activation in disc degeneration and the role of degenerated tissue in complement activation.
Article
Chemistry, Medicinal
Hikaru Tamura, Tomoki Maekawa, Hisanori Domon, Kridtapat Sirisereephap, Toshihito Isono, Satoru Hirayama, Takumi Hiyoshi, Karin Sasagawa, Fumio Takizawa, Takeyasu Maeda, Yutaka Terao, Koichi Tabeta
Summary: Inflammatory tissues are affected by the macrolide erythromycin (ERM), which inhibits excessive neutrophil accumulation and bone resorption. This study investigates the osteoblastogenic effect of ERM through upregulation of DEL-1 in inflammatory conditions. The results suggest that ERM treatment increases DEL-1 expression and suppresses bone loss by increasing the expression of osteoblast-associated factors.
Article
Dentistry, Oral Surgery & Medicine
M. Arce, M. Rodriguez-Pena, J. Espinoza-Arrue, R. A. Godoy, M. Reyes, T. Kajikawa, T. Greenwell-Wild, G. Hajishengallis, L. Abusleme, N. Moutsopoulos, N. Dutzan
Summary: Periodontitis is a common inflammatory disease characterized by tissue destruction. This study found that cytokines such as IL-6 and IL-23, which are associated with tissue destruction, use a signaling pathway mediated by STAT3. STAT3 activation was found to be increased in epithelial cells and T cells during periodontitis.
JOURNAL OF DENTAL RESEARCH
(2023)
Review
Immunology
Dimitrios C. Mastellos, George Hajishengallis, John D. Lambris
Summary: Complement, previously considered as a crucial innate immune effector, is now known to have broader involvement in fundamental biological processes beyond innate immunity. It engages in intricate crosstalk with various pathways and regulates processes like development, tissue regeneration, and cancer immunity. Dysregulation of complement activation can lead to inflammatory tissue pathology, but this understanding has also inspired the development of complement-based therapeutics.
NATURE REVIEWS IMMUNOLOGY
(2023)
Review
Microbiology
George Hajishengallis
Summary: Periodontitis and caries are influenced by complex interactions between the oral microbiome and host factors. Animal models have been valuable in understanding the mechanisms of these diseases, although no single model can fully replicate human diseases. This review emphasizes the importance of animal models in proving causality, identifying therapeutic targets, and evaluating novel treatments. Combining animal model-derived findings with in vitro and clinical research can provide a deeper understanding of oral disease pathogenesis.
FEMS MICROBIOLOGY REVIEWS
(2023)
