Article
Immunology
Aleksandra Wielento, Grzegorz P. Bereta, Katarzyna B. Lagosz-Cwik, Sigrun Eick, Richard J. Lamont, Aleksander M. Grabiec, Jan Potempa
Summary: PPAD and fimbriae from P. gingivalis are important for TLR2-dependent host cell responses, contributing to the generation of inflammatory responses.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Dentistry, Oral Surgery & Medicine
Aleksandra Wielento, Grzegorz P. Bereta, Katarzyna Szczesniak, Anna Jacula, Marina Terekhova, Maxim N. Artyomov, Yoshiaki Hasegawa, Aleksander M. Grabiec, Jan Potempa
Summary: Porphyromonas gingivalis, an oral pathogen, promotes dysbiosis by suppressing the bactericidal activity of the host immune system and maintaining chronic inflammation. It activates Toll-like receptor 2 (TLR2) through the secretion of virulence factors such as P. gingivalis peptidyl arginine deiminase (PPAD) and major fimbriae (FimA). PPAD-modified fimbriae trigger the host cell response, and accessory fimbrial subunits are modified by PPAD and stimulate the response to P. gingivalis infection in a TLR2-dependent manner.
MOLECULAR ORAL MICROBIOLOGY
(2023)
Article
Cell Biology
Zeyuan Gao, Xiuhong Weng, Donghu Yu, Zhiyong Pan, Mingjuan Zhao, Bo Cheng, Zhiqiang Li
Summary: Periodontitis is significantly associated with the risk of lung and digestive system cancers, as well as potentially various brain diseases. A study found that P. gingivalis LPS can promote glioma cell proliferation and migration, and increase levels of TNF-alpha, TGF-beta, MMP2, MMP9, and phosphorylation of Akt. Poor periodontal status was significantly higher in glioma patients compared to those with benign tumors, suggesting a possible association between periodontal infection and glioma progression.
Article
Oncology
Shegan Gao, Ke Liu, Yelin Jiao, Pan Chen, Bianli Gu, Yiwen Liu, Gaofeng Liang, Linlin Shi, Fuyou Zhou, Richard J. Lamont, Huizhi Wang, Yi-Jun Qi
Summary: This study found that Porphyromonas gingivalis infection increased TGF13 secretion and activated TGF13/Smad signaling in esophageal squamous cell carcinoma (ESCC). It also demonstrated that P. gingivalis enhanced the expression of GARP, which further activated TGF13/Smad signaling. The activation of TGF13 signaling was found to be associated with poor prognosis in ESCC patients. Targeting either P. gingivalis or GARP-TGF13 signaling could be a potential treatment strategy for ESCC.
AMERICAN JOURNAL OF CANCER RESEARCH
(2023)
Review
Dentistry, Oral Surgery & Medicine
Yoshiaki Hasegawa, Keiji Nagano
Summary: Porphyromonas gingivalis, a periodontal pathogen, expresses distinct FimA and Mfa1 fimbriae, which play important roles in host cells and other oral bacterial species. Studies have shown a correlation between the pathogenicity of P. gingivalis and the fimA genotype, but not the mfa1 genotype. Recent research provides new insights into the structure, function, and biogenesis of these fimbrial proteins.
JAPANESE DENTAL SCIENCE REVIEW
(2021)
Article
Microbiology
Miyuna Fujimoto, Yoshikazu Naiki, Kotaro Sakae, Tomohiko Iwase, Naoyoshi Miwa, Keiji Nagano, Hiroyuki Nawa, Yoshiaki Hasegawa
Summary: The Mfa1 fimbriae of Porphyromonas gingivalis, a pathogen that causes periodontal disease, are responsible for biofilm formation and consist of five proteins. Two major genotypes, mfa1(70) and mfa1(53), encode the major fimbrillin protein. The mfa1(70) genotype can be further divided into the mfa1(70A) and mfa1(70B) subtypes.
JOURNAL OF ORAL MICROBIOLOGY
(2023)
Article
Biochemical Research Methods
Yancong Zhang, Kelsey N. Thompson, Curtis Huttenhower, Eric A. Franzosa
Summary: Researcher designed and evaluated statistical models in metatranscriptomics that incorporate different combinations of DNA and RNA normalization, finding that models adjusting transcripts relative to their encoding gene copies are significantly more accurate in identifying differential expression. Additionally, normalization of MTX measurements within species and adjusting for total species RNA balance can improve sensitivity, specificity, and interpretability of DE detection.
Article
Immunology
Che Qiu, Zhen Yuan, Zhiyan He, Huiwen Chen, Yue Liao, Shiliang Li, Wei Zhou, Zhongchen Song
Summary: The study demonstrates that P. gingivalis-LPS can induce an inflammatory response in microglial cells through TLR2/4-mediated NF-kappa B/STAT3 signaling pathways. Compared to E. coli-LPS, P. gingivalis-LPS is a weaker activator, possibly due to structural differences in fatty acid chains and phosphate groups.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yuki Suzuki, Takeshi Kikuchi, Hisashi Goto, Yuhei Takayanagi, Shotaro Kawamura, Noritaka Sawada, Yoshikazu Naiki, Hisataka Kondo, Jun-ichiro Hayashi, Yoshiaki Hasegawa, Akio Mitani
Summary: The effect of Mfa1 fimbriae from Porphyromonas gingivalis on bone resorption progression and its interaction with Toll-like receptors (TLRs) were investigated in this study. The results showed that Mfa1 fimbriae effectively induced the formation and activation of osteoclasts, as well as increased the expression of specific genes related to differentiation. The involvement of Tlr2 and Tlr4 in Mfa1 recognition was also demonstrated. These findings contribute to the understanding of the mechanisms underlying periodontal disease and the development of potential therapeutic strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Microbiology
Anna Gasiorek, Ewelina Dobosz, Barbara Potempa, Izabela Ciaston, Mateusz Wilamowski, Zuzanna Oruba, Richard J. Lamont, Jolanta Jura, Jan Potempa, Joanna Koziel
Summary: Periodontal disease is an inflammatory disease of the supporting tissues of the teeth caused by dysbiotic biofilm on the tooth surface. The negative regulator MCPIP-1 plays a key role in controlling inflammatory responses, but its stability can be influenced by periodontal pathogens like Porphyromonas gingivalis. The proteolytic activity of gingipains from these pathogens can lead to rapid degradation of MCPIP-1, exacerbating the inflammatory response. This provides insights into potential new treatment strategies for periodontitis.
Article
Immunology
Ye Zhang, Wei Kuang, Danfeng Li, Yu Li, Yi Feng, Xinwei Lyu, Gao-Bo Huang, Jian-Qi Lian, Xiao-Fei Yang, Cheng Hu, Yajuan Xie, Song Xue, Jiali Tan
Summary: NKB cells play a crucial role in periodontitis by secreting IL-18 to promote inflammation and bone resorption. Elevated levels of NKB cells and IL-18 were observed in periodontitis patients and correlated with attachment loss. Additionally, IL-18 stimulation led to proinflammatory cytokine production in periodontal ligament cells, suggesting a potential target for immunotherapies in periodontitis.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Dentistry, Oral Surgery & Medicine
Qingli Chen, Zhe Shao, Ke Liu, Xiaocheng Zhou, Lin Wang, Erhui Jiang, Tingting Luo, Zhengjun Shang
Summary: This study found that Pg may be involved in the pathogenesis of OSCC, patients with OSCC carried prevalent fimA genotypes I, Ib, II, and IV, Pg in OSCC tissue may originate from the salivary microbial reservoir, and the abundance of Pg in saliva could be considered as a potentially favorable prognostic indicator in OSCC.
Article
Dentistry, Oral Surgery & Medicine
Mari Fujita, Chen-Hsuan Chiu, Keiji Nagano
Summary: The Mfa1 fimbria of Porphyromonas gingivalis is composed of multiple proteins encoded by different genes, which are arranged in tandem on the chromosomes. This study investigated the transcriptional unit and activity of mfa genes in strains with one or two mfa5 genes. The results showed that mfa1 had higher transcription levels compared to mfa2 in all strains, while mfa2 to mfa5 showed comparable expression. In certain strains, both mfa5 genes were transcribed at similar levels. Additionally, analysis identified a transcriptional terminator structure in the intergenic region between mfa1 and mfa2 that may influence the transcription rate of mfa2 and downstream genes.
MOLECULAR ORAL MICROBIOLOGY
(2023)
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
Ji-Won Kim, Hyerin Jung, In-Pyo Baek, Yoojun Nam, Jaewoo Kang, Min Kyung Chung, Jun-Beom Park, Jennifer Lee, Seung-Ki Kwok, Wan-Uk Kim, Sung-Hwan Park, Ji Hyeon Ju
Summary: Periodontal bacteria may shape RF status by affecting the humoral immune response during RA pathogenesis.
SCIENTIFIC REPORTS
(2022)
Article
Dentistry, Oral Surgery & Medicine
G. Yuan, C. Fu, S. T. Yang, D. Y. Yuh, G. Hajishengallis, S. Yang
Summary: Ablation of RGS12 in hematopoietic cells was shown to prevent bone loss in a periodontitis model, inhibit osteoclast formation and activity, and reduce inflammatory cytokine production in periodontal tissue. In vitro experiments also demonstrated that overexpression of RGS12 promoted proinflammatory macrophage reprogramming and enhanced migration ability, while knockdown of RGS12 inhibited inflammatory cytokine production and macrophage migration in response to stimuli like lipopolysaccharide. The results suggest that targeting RGS12 in macrophages could be a promising therapeutic approach for periodontitis.
JOURNAL OF DENTAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Xiaofei Li, Hui Wang, Xiang Yu, Gundappa Saha, Lydia Kalafati, Charalampos Ioannidis, Ioannis Mitroulis, Mihai G. Netea, Triantafyllos Chavakis, George Hajishengallis
Summary: Bone marrow-mediated trained innate immunity can enhance immune responsiveness, but maladaptive training can lead to inflammatory comorbidities. Periodontitis can induce maladaptive trained phenotype in the bone marrow, resulting in increased production of myeloid cells with inflammatory preparedness. The trained phenotype of the bone marrow can be transmitted to naive recipients through transplantation and lead to increased inflammatory responsiveness and disease severity. Inhibiting IL-1 signaling can prevent maladaptive training caused by periodontitis.
Review
Dentistry, Oral Surgery & Medicine
George Hajishengallis, Xiaofei Li, Kimon Divaris, Triantafyllos Chavakis
Summary: This article reviews the bidirectional association between periodontitis and systemic inflammatory disorders. It introduces two newly emerged concepts, trained innate immunity (TII) and clonal hematopoiesis of indeterminate potential (CHIP), which together support a potential hypothesis on how periodontitis affects and is affected by comorbidities and why the susceptibility to periodontitis and comorbidities increases with aging. The article discusses the role of TII and CHIP in mediating the relationship between periodontitis and comorbidities, and proposes that a mechanistic understanding of this connection may lead to novel diagnostic and therapeutic targets for inflammatory comorbidities.
PERIODONTOLOGY 2000
(2022)
Article
Dentistry, Oral Surgery & Medicine
G. Hajishengallis, T. Chavakis
Summary: Neutrophils are important cells that play a role in both inflammatory response and maintaining tissue homeostasis. They can be both protective and destructive, depending on the context. Local tissue factors and systemic metabolic conditions can regulate the activity and production of neutrophils. Targeted therapeutic interventions can be developed based on current insights to restrain neutrophil-mediated inflammation in chronic inflammatory diseases.
JOURNAL OF DENTAL RESEARCH
(2022)
Review
Immunology
Tetsuhiro Kajikawa, Dimitrios C. Mastellos, Hatice Hasturk, Georgios A. Kotsakis, Despina Yancopoulou, John D. Lambris, George Hajishengallis
Summary: Periodontitis, if not properly treated, can lead to tooth loss and affect overall health. This review focuses on the potential use of a complement-targeting drug called AMY-101 in the treatment of periodontal disease and peri-implant inflammatory conditions.
SEMINARS IN IMMUNOLOGY
(2022)
Editorial Material
Immunology
Drake W. Williams, George Hajishengallis, Niki M. Moutsopoulos
Summary: The study expands our understanding of immune responses during oral infection, shedding light on the regional specialization of oral immunity.
SCIENCE IMMUNOLOGY
(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)
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
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)
Article
Dentistry, Oral Surgery & Medicine
Elan Zebrowitz, Azamat Aslanukov, Tetsuhiro Kajikawa, Kamila Bedelbaeva, Sam Bollinger, Yong Zhang, David Sarfatti, Jing Cheng, Phillip B. Messersmith, George Hajishengallis, Ellen Heber-Katz
Summary: This study explores a specific case of volumetric bone loss in a mouse model, where bone and soft tissues are restored through a regenerative response induced by a small molecule inhibitor, indicating potential therapeutic possibilities.
FRONTIERS IN DENTAL MEDICINE
(2022)
Review
Dentistry, Oral Surgery & Medicine
Georgios N. N. Belibasakis, George Hajishengallis
Summary: The 2nd International Conference on Oral Mucosal Immunity and the Microbiome (OMIM) was held successfully with the participation of 29 international speakers. This conference, being the first conference travel in the post-pandemic era, holds significant importance for academic exchange in the field of oral health.
FRONTIERS IN ORAL HEALTH
(2022)