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State-of-the-Art Molecular Immunology in Chile

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (30 December 2022) | Viewed by 36926

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Special Issue Editors

Prof. Dr. Marcela Hernandez Ríos

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1. Laboratory of Periodontal Biology, Faculty of Dentistry, University of Chile, Santiago 8380544, Chile
2. Department of Pathology and Oral Medicine, Faculty of Dentistry, University of Chile, Santiago 8380544, Chile
Interests: host–pathogen interactions; periodontitis; endodontics; oral medicine
Special Issues, Collections and Topics in MDPI journals

Dr. Juan C. Aguillon

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Guest Editor

Immune Regulation and Tolerance Research Group, Immunology Program, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 7800003, Chile
Interests: autoantigen discovery; rheumatoid arthritis; dendritic cells
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Dr. María Rosa Bono

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Departamento de Biología, Facultad de Ciencias, Universidad de Chile, Santiago 7800003, Chile
Interests: basic immunology and autoimmunity
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Dr. Leandro J. Carreño

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Millennium Institute on Immunology and Immunotherapy, Programa de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile
Interests: natural killer T cells; T cells; B cells; inflammation; allergy
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Prof. Dr. Rolando Vernal

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Periodontal Biology Laboratory, Faculty of Dentistry, Universidad de Chile, Santiago 8380492, Chile
Interests: osteoimmunology; dentistry; oral microbiology; alveolar bone loss; alveolar bone resorption; alveolar bone regeneration
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Dr. Nicolas Dutzan

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Guest Editor

1. Laboratory of Oral Microbiology, Faculty of Dentistry, University of Chile, Santiago 7800003, Chile
2. Conservative Dentistry Department, Faculty of Dentistry, University of Chile, Santiago 7800003, Chile
Interests: mucosal immunology; cytokines; T helper cells; oral mucosa; periodontitis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The immune system is a highly integrated array of molecular and cellular components that have evolved to protect the host from disease. Its functions are divided up into two main arms: the innate immune system, as the first line of non-specific defense; and the adaptive immune system, involving enhanced responses to specific pathogens, cells, or foreign substances. If the immune balance is disturbed, it can lead to disease. Molecular-level basic and clinical research in this area involves autoimmunity, immunodeficiency, allergies, infectious-inflammatory diseases, neuroimmunology, and cancer. Additionally, the emerging knowledge of the immune system contributes to developing new therapies, such as immunotherapy, monoclonal antibodies, and vaccines, which either block or prime the immune system to manage or eliminate the disease. This Special Issue of IJMS aims to provide a comprehensive view of Recent Advances in Molecular Immunology in Chile. We invite research and review papers that will consolidate our understanding in this area. Potential topics include, but are not limited to, the following:

Host–pathogen interactions
Innate immunity
Adaptive immunity
Immunopathology
Cancer immunology
Neuroimmunology
Osteoimmunology
Immunosenescence
Immunomodulation
Immunotherapy
Antibody therapy
Vaccines

Prof. Dr. Marcela Hernandez Ríos
Dr. Juan C. Aguillon
Dr. María Rosa Bono
Dr. Leandro J. Carreño
Dr. Rolando Vernal
Dr. Nicolas Dutzan
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

innate immunity
adaptive immunity
host-pathogen interactions
immunopathology
osteoimmunology
immunosenescence
immunotherapy
antibody
vaccines
Chile

Published Papers (13 papers)

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15 pages, 2970 KiB

Open AccessArticle

Levels of Pro-Inflammatory and Bone-Resorptive Mediators in Periodontally Compromised Patients under Orthodontic Treatment Involving Intermittent Forces of Low Intensities

by Cristian Navarrete, Alejandro Riquelme, Natalia Baksai, Romina Pérez, Claudia González, María Michea, Hans von Mühlenbrock, Emilio A. Cafferata and Rolando Vernal

Int. J. Mol. Sci. 2023, 24(5), 4807; https://doi.org/10.3390/ijms24054807 - 2 Mar 2023

Viewed by 1808

Abstract

During orthodontic treatment, diverse cytokines, enzymes, and osteolytic mediators produced within the teeth surrounding periodontal tissues determine the rate of alveolar bone remodeling and consequent teeth movement. In patients with teeth presenting reduced periodontal support, periodontal stability should be ensured during orthodontic treatment. Thus, therapies based on the application of low-intensity intermittent orthodontic forces are recommended. To determine if this kind of treatment is periodontally well tolerated, this study aimed to analyze the production of receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), interleukin (IL)-6, IL-17A, and matrix metalloproteinase (MMP)-8 in periodontal tissues of protruded anterior teeth with reduced periodontal support and undergoing orthodontic treatment. Patients with periodontitis-associated anterior teeth migration received non-surgical periodontal therapy and a specific orthodontic treatment involving controlled low-intensity intermittent orthodontic forces. Samples were collected before periodontitis treatment, after periodontitis treatment, and at 1 week to 24 months of the orthodontic treatment. During the 2 years of orthodontic treatment, no significant differences were detected in the probing depth, clinical attachment level, supragingival bacterial plaque, and bleeding on probing. In line with this, the gingival crevicular levels of RANKL, OPG, IL-6, IL-17A, and MMP-8 did not vary between the different evaluation time-points of the orthodontic treatment. When compared with the levels detected during the periodontitis, the RANKL/OPG ratio was significantly lower at all the analyzed time-points of the orthodontic treatment. In conclusion, the patient-specific orthodontic treatment based on intermittent orthodontic forces of low intensities was well tolerated by periodontally compromised teeth with pathological migration. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Immunology in Chile)

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21 pages, 5169 KiB

Open AccessArticle

Analysis of Tumor-Infiltrating T-Cell Transcriptomes Reveal a Unique Genetic Signature across Different Types of Cancer

by Mabel Vidal, Marco Fraga, Faryd Llerena, Agustín Vera, Mauricio Hernández, Elard Koch, Felipe Reyes-López, Eva Vallejos-Vidal, Guillermo Cabrera-Vives and Estefanía Nova-Lamperti

Int. J. Mol. Sci. 2022, 23(19), 11065; https://doi.org/10.3390/ijms231911065 - 21 Sep 2022

Cited by 4 | Viewed by 2743

Abstract

CD8+ and CD4+ T-cells play a key role in cellular immune responses against cancer by cytotoxic responses and effector lineages differentiation, respectively. These subsets have been found in different types of cancer; however, it is unclear whether tumor-infiltrating T-cell subsets exhibit similar transcriptome profiling across different types of cancer in comparison with healthy tissue-resident T-cells. Thus, we analyzed the single cell transcriptome of five tumor-infiltrating CD4-T, CD8-T and Treg cells obtained from different types of cancer to identify specific pathways for each subset in malignant environments. An in silico analysis was performed from single-cell RNA-sequencing data available in public repositories (Gene Expression Omnibus) including breast cancer, melanoma, colorectal cancer, lung cancer and head and neck cancer. After dimensionality reduction, clustering and selection of the different subpopulations from malignant and nonmalignant datasets, common genes across different types of cancer were identified and compared to nonmalignant genes for each T-cell subset to identify specific pathways. Exclusive pathways in CD4+ cells, CD8+ cells and Tregs, and common pathways for the tumor-infiltrating T-cell subsets were identified. Finally, the identified pathways were compared with RNAseq and proteomic data obtained from T-cell subsets cultured under malignant environments and we observed that cytokine signaling, especially Th2-type cytokine, was the top overrepresented pathway in Tregs from malignant samples. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Immunology in Chile)

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12 pages, 2286 KiB

Open AccessArticle

Exploring the Expression of Pro-Inflammatory and Hypoxia-Related MicroRNA-20a, MicroRNA-30e, and MicroRNA-93 in Periodontitis and Gingival Mesenchymal Stem Cells under Hypoxia

by Alejandra Chaparro, Mauricio Lozano, Dominique Gaedechens, Carolina López, Daniela Albers, Marcela Hernández, Andrés Pascual, José Nart and Carlos E. Irarrazabal

Int. J. Mol. Sci. 2022, 23(18), 10310; https://doi.org/10.3390/ijms231810310 - 7 Sep 2022

Cited by 3 | Viewed by 1963

Abstract

Hypoxia associated with inflammation are common hallmarks observed in several diseases, and it plays a major role in the expression of non-coding RNAs, including microRNAs (miRNAs). In addition, the miRNA target genes for hypoxia-inducible factor-1α (HIF-1α) and nuclear factor of activated T cells-5 (NFAT5) modulate the adaptation to hypoxia. The objective of the present study was to explore hypoxia-related miRNA target genes for HIF-1α and NFAT5, as well as miRNA-20a, miRNA-30e, and miRNA-93 expression in periodontitis versus healthy gingival tissues and gingival mesenchymal stem cells (GMSCs) cultured under hypoxic conditions. Thus, a case-control study was conducted, including healthy and periodontitis subjects. Clinical data and gingival tissue biopsies were collected to analyze the expression of miRNA-20a, miRNA-30e, miRNA-93, HIF-1α, and NFAT5 by qRT-PCR. Subsequently, GMSCs were isolated and cultured under hypoxic conditions (1% O₂) to explore the expression of the HIF-1α, NFAT5, and miRNAs. The results showed a significant upregulation of miRNA-20a (p = 0.028), miRNA-30e (p = 0.035), and miRNA-93 (p = 0.026) in periodontitis tissues compared to healthy gingival biopsies. NFAT5 mRNA was downregulated in periodontitis tissues (p = 0.037), but HIF-1α was not affected (p = 0.60). Interestingly, hypoxic GMSCs upregulated the expression of miRNA-20a and HIF-1α, but they downregulated miRNA-93e. In addition, NFAT5 mRNA expression was not affected in hypoxic GMSCs. In conclusion, in periodontitis patients, the expression of miRNA-20a, miRNA-30e, and miRNA-93 increased, but a decreased expression of NFAT5 mRNA was detected. In addition, GMSCs under hypoxic conditions upregulate the HIF-1α and increase miRNA-20a (p = 0.049) expression. This study explores the role of inflammatory and hypoxia-related miRNAs and their target genes in periodontitis and GMSCs. It is crucial to determine the potential therapeutic target of these miRNAs and hypoxia during the periodontal immune–inflammatory response, which should be analyzed in greater depth in future studies. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Immunology in Chile)

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15 pages, 1978 KiB

Open AccessArticle

Lipopolysaccharide from Porphyromonas gingivalis, but Not from Porphyromonas endodontalis, Induces Macrophage M1 Profile

by Pablo Veloso, Alejandra Fernández, Jessica Astorga, David González-Quintanilla, Alfredo Castro, Alejandro Escobar, Anilei Hoare and Marcela Hernández

Int. J. Mol. Sci. 2022, 23(17), 10011; https://doi.org/10.3390/ijms231710011 - 2 Sep 2022

Cited by 4 | Viewed by 2138

Abstract

Apical Lesions of Endodontic Origin (ALEO) are initiated by polymicrobial endodontic canal infection. Porphyromonas gingivalis (Pg) and Porphyromonas endodontalis (Pe) lipopolysaccharides (LPS) can induce a pro-inflammatory macrophage response through their recognition by TLR2 and TLR4. However, polarization responses induced by Pg and/or Pe LPS in macrophages are not fully understood. We aimed to characterize the polarization profiles of macrophages differentiated from THP-1 cells following Pg and/or Pe LPS stimulation from reference strain and clinical isolates. A modified LPS purification protocol was implemented and the electrophoretic LPS profiles were characterized. THP-1 human monocytes differentiated to macrophages were stimulated with Pg and Pe LPS. Polarization profiles were characterized through cell surface markers and secreted cytokines levels after 24 h of stimulation. TLR2 and TLR4 cell surfaces and transcriptional levels were determined after 24 or 2 h of LPS stimulation, respectively. LPS from Pg induced a predominant M1 profile in macrophages evidenced by changes in the expression of the surface marker CD64 and pro-inflammatory cytokine profiles, TNF-α, IL-1β, IL-6, and IL-12. Pe LPS was unable to induce a significant response. TLR2 and TLR4 expressions were neither modified by Pg or Pe LPS. Pg LPS, but not Pe LPS, induced a macrophage M1 Profile. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Immunology in Chile)

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11 pages, 678 KiB

Open AccessArticle

MMP-9 Levels in the Gingival Crevicular Fluid of Chilean Rosacea Patients

by Javier Fernández, Constanza Jiménez, Dafna Benadof, Paulina Morales, Jessica Astorga, Felipe Cáceres, Marcela Hernández, Alejandra Fernández and Fernando Valenzuela

Int. J. Mol. Sci. 2022, 23(17), 9858; https://doi.org/10.3390/ijms23179858 - 30 Aug 2022

Cited by 2 | Viewed by 1593

Abstract

Rosacea is a chronic inflammatory skin disease whose prevalence rates remain unknown in Chile. Laboratory benchmark testing for this disease is not useful, therefore, we aimed to evaluate the gingival crevicular fluid (GCF) levels of extracellular metalloproteinases (MMP)-2 and MMP-9 as novel rosacea biomarkers. We designed a cross-sectional study with a control group. Participants were systemically healthy adults (n = 20) and persons with rosacea (n = 18). We performed a periodontal evaluation and collected gingival crevicular fluid to measure MMP-2 and MMP-9 levels. Analysis showed mean and standard deviation of MMP-9 concentrations in the GCF for patients with rosacea was 764.52 ± 569.83 pg/mL; for healthy patients, it was 260.69 ± 170.43 pg/mL (p < 0.05). The diagnosis of rosacea was responsible for the levels of MMP-9 in the GCF (p < 0.05), as opposed to periodontitis, smoking, and age (p > 0.05). The Area under ROC for MMP-9 was 0.869 (95%, C.I: 0.719–0.956), with a sensitivity of 72.22% and specificity of 81.58% for the diagnosis of rosacea. We conclude that the quantification of MMP-9 in the GCF could be used as a biomarker of rosacea. Also, rosacea was responsible for increasing the levels of MMP-9 in the GCF independent of periodontal status. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Immunology in Chile)

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8 pages, 271 KiB

Open AccessArticle

Molecular Biomarkers in Peri-Implant Health and Disease: A Cross-Sectional Pilot Study

by Alejandra Chaparro, Víctor Beltrán, Daniel Betancur, Ye-Han Sam, Haniyeh Moaven, Ali Tarjomani, Nikolaos Donos and Vanessa Sousa

Int. J. Mol. Sci. 2022, 23(17), 9802; https://doi.org/10.3390/ijms23179802 - 29 Aug 2022

Cited by 7 | Viewed by 1774

Abstract

Background: The aim of this feasibility study was to investigate the concentration level of CCL-20/MIP-3α, BAFF/BLyS, IL-23, RANKL, and Osteoprotegerin in the Peri-Implant Crevicular Fluid (PICF), from patients diagnosed with peri-implant mucositis and peri-implantitis, and to compare them with PICF from patients with healthy implants. Methods: Participants with at least one dental implant with healthy peri-implant tissues, peri-implant mucositis, or peri-implantitis were included. PICF was collected using paper strips from healthy and diseased peri-implant sites (n = 19). Biomarker levels were analyzed using a custom Multiplex ELISA Assay Kit. Results: In comparison to peri-implant health, the peri-implant mucositis group showed an increased concentration of CCL-20 MIP-3α, BAFF/BLyS, IL-23, RANKL, and Osteoprotegerin. The peri-implantitis group had the lowest median concentration of Osteoprotegerin (1963 ng/mL); this group had a similar concentration of RANKL (640.84 ng/mL) when compared to the peri-implant health group. BAFF/BLyS (17.06 ng/mL) showed the highest concentration in the peri-implantitis group. Conclusions: This feasibility study suggests that IL-23 and RANKL may help to elucidate the pathogenesis during the conversion from peri-implant health to peri-implantitis. Further research is required in BAFF/BLyS for the early diagnosis of peri-implantitis. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Immunology in Chile)

18 pages, 3017 KiB

Open AccessArticle

TNF-α Affects Signature Cytokines of Th1 and Th17 T Cell Subsets through Differential Actions on TNFR1 and TNFR2

by Bárbara Pesce, Carolina H. Ribeiro, Milton Larrondo, Verónica Ramos, Lilian Soto, Diego Catalán and Juan Carlos Aguillón

Int. J. Mol. Sci. 2022, 23(16), 9306; https://doi.org/10.3390/ijms23169306 - 18 Aug 2022

Cited by 10 | Viewed by 1856

Abstract

Tumor necrosis factor (TNF)-α is a pleiotropic cytokine implicated in the etiology of several autoimmune diseases, including rheumatoid arthritis (RA). TNF-α regulates diverse effector functions through the activation of TNF-α receptor (TNFR)1 and TNFR2. Although the detrimental role of this cytokine has been addressed in distinct disease settings, the effects of TNF-α on cytokine production by isolated CD4⁺ T helper type 1 (Th1) and Th17 cells, two T cell subpopulations that contribute to the pathogenesis of RA, have not been completely elucidated. Here, we show that TNF-α promotes a reduction and expansion in the frequency of both T cell subsets producing IFN-γ and IL-17, respectively. Selective blockade of TNFR1 or TNFR2 on Th1 and Th17 cells revealed that TNFR2 mediates the decrease in IFN-γ production, while signaling through both receptors augments IL-17 production. We also demonstrate that Th1, but not Th17 cells from RA patients present lower levels of TNFR1 compared to healthy controls, whereas TNFR2 expression on both T cell types is similar between patients and controls. Since TNF-α receptors levels in RA patients are not significantly changed by the therapeutic blockade of TNF-α, we propose that targeting TNFR2 may represent an alternative strategy to normalize the levels of key cytokines that contribute to RA pathogenesis. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Immunology in Chile)

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Review

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16 pages, 2620 KiB

Open AccessReview

Contribution of −Omics Technologies in the Study of Porphyromonas gingivalis during Periodontitis Pathogenesis: A Minireview

by Josefa Nuñez-Belmar, Mauricio Morales-Olavarria, Emiliano Vicencio, Rolando Vernal, Juan P. Cárdenas and Cristian Cortez

Int. J. Mol. Sci. 2023, 24(1), 620; https://doi.org/10.3390/ijms24010620 - 30 Dec 2022

Cited by 7 | Viewed by 3452

Abstract

Periodontitis is a non-communicable chronic inflammatory disease characterized by the progressive and irreversible breakdown of the soft periodontal tissues and resorption of teeth-supporting alveolar bone. The etiology of periodontitis involves dysbiotic shifts in the diversity of microbial communities inhabiting the subgingival crevice, which is dominated by anaerobic Gram-negative bacteria, including Porphyromonas gingivalis. Indeed, P. gingivalis is a keystone pathogen with a repertoire of attributes that allow it to colonize periodontal tissues and influence the metabolism, growth rate, and virulence of other periodontal bacteria. The pathogenic potential of P. gingivalis has been traditionally analyzed using classical biochemical and molecular approaches. However, the arrival of new techniques, such as whole-genome sequencing, metagenomics, metatranscriptomics, proteomics, and metabolomics, allowed the generation of high-throughput data, offering a suitable option for bacterial analysis, allowing a deeper understanding of the pathogenic properties of P. gingivalis and its interaction with the host. In the present review, we revise the use of the different −omics technologies and techniques used to analyze bacteria and discuss their potential in studying the pathogenic potential of P. gingivalis. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Immunology in Chile)

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30 pages, 5234 KiB

Open AccessReview

The Relationship between Reactive Oxygen Species and the cGAS/STING Signaling Pathway in the Inflammaging Process

by Bárbara Andrade, Carlos Jara-Gutiérrez, Marilyn Paz-Araos, Mary Carmen Vázquez, Pablo Díaz and Paola Murgas

Int. J. Mol. Sci. 2022, 23(23), 15182; https://doi.org/10.3390/ijms232315182 - 2 Dec 2022

Cited by 19 | Viewed by 3949

Abstract

During Inflammaging, a dysregulation of the immune cell functions is generated, and these cells acquire a senescent phenotype with an increase in pro-inflammatory cytokines and ROS. This increase in pro-inflammatory molecules contributes to the chronic inflammation and oxidative damage of biomolecules, classically observed in the Inflammaging process. One of the most critical oxidative damages is generated to the host DNA. Damaged DNA is located out of the natural compartments, such as the nucleus and mitochondria, and is present in the cell’s cytoplasm. This DNA localization activates some DNA sensors, such as the cGAS/STING signaling pathway, that induce transcriptional factors involved in increasing inflammatory molecules. Some of the targets of this signaling pathway are the SASPs. SASPs are secreted pro-inflammatory molecules characteristic of the senescent cells and inducers of ROS production. It has been suggested that oxidative damage to nuclear and mitochondrial DNA generates activation of the cGAS/STING pathway, increasing ROS levels induced by SASPs. These additional ROS increase oxidative DNA damage, causing a loop during the Inflammaging. However, the relationship between the cGAS/STING pathway and the increase in ROS during Inflammaging has not been clarified. This review attempt to describe the potential connection between the cGAS/STING pathway and ROS during the Inflammaging process, based on the current literature, as a contribution to the knowledge of the molecular mechanisms that occur and contribute to the development of the considered adaptative Inflammaging process during aging. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Immunology in Chile)

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16 pages, 1596 KiB

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Neutrophil N1 and N2 Subsets and Their Possible Association with Periodontitis: A Scoping Review

by Luis Daniel Sansores-España, Samanta Melgar-Rodríguez, Rolando Vernal, Bertha Arelly Carrillo-Ávila, Víctor Manuel Martínez-Aguilar and Jaime Díaz-Zúñiga

Int. J. Mol. Sci. 2022, 23(20), 12068; https://doi.org/10.3390/ijms232012068 - 11 Oct 2022

Cited by 7 | Viewed by 3138

Abstract

Periodontitis is a chronic non-communicable disease caused by dysbiotic changes that affect the subgingival microbiota. During periodontitis, neutrophils play a central role in the initial recognition of bacteria, and their number increases with the appearance of the first signs of periodontal inflammation. Recent evidence has led to the proposition that neutrophils can also functionally polarize, determining selective activity patterns related to different diseases. Two well-defined neutrophil phenotypes have been described, the pro-inflammatory N1 subset and the suppressor N2 subset. To date, it has not been established whether these different neutrophil subtypes play a role in the pathogenesis of periodontitis. Thus, this scoping review aimed to determine whether there was evidence to suggest that the neutrophils present in periodontal tissues can be associated with certain phenotypes. The research question, population, concept, and context sought to identify original articles, in humans, that detected the presence of neutrophils in the periodontal tissues of people affected by periodontitis. Based on the search strategy, we found 3658 studies. After removing the papers with abstracts not related to the outcome measures and eligibility criteria, 16 articles were included for qualitative analysis. Several studies identified the presence of different neutrophil subsets, specifically, the naive, pro- and para-inflammatory, hyper-reactive and hyper-active, and high- and low-responder phenotypes. The existing evidence demonstrates the presence of pro-inflammatory, hyper-reactive and high-responder neutrophils in periodontal tissues affected with periodontitis. There is no evidence demonstrating the presence of the N1 or N2 phenotypes in periodontal tissues during periodontitis. However, the existence of pro-inflammatory phenotypes, which increase NETosis and degranulation, and increase the production of pro-inflammatory cytokines, could be suggestive of the N1 phenotypes. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Immunology in Chile)

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18 pages, 1234 KiB

Open AccessReview

Biomarkers of Periodontitis and Its Differential DNA Methylation and Gene Expression in Immune Cells: A Systematic Review

by Angélica M. Cárdenas, Laura J. Ardila, Rolando Vernal, Samanta Melgar-Rodríguez and Hernán G. Hernández

Int. J. Mol. Sci. 2022, 23(19), 12042; https://doi.org/10.3390/ijms231912042 - 10 Oct 2022

Cited by 8 | Viewed by 2941

Abstract

The characteristic epigenetic profile of periodontitis found in peripheral leukocytes denotes its impact on systemic immunity. In fact, this profile not only stands for periodontitis as a low-grade inflammatory disease with systemic effects but also as an important source of potentially valuable clinical biomarkers of its systemic effects and susceptibility to other inflammatory conditions. Thus, we aimed to identify relevant genes tested as epigenetic systemic biomarkers in patients with periodontitis, based on the DNA methylation patterns and RNA expression profiles in peripheral immune cells. A detailed protocol was designed following the Preferred Reporting Items for Systematic Review and Meta-analysis -PRISMA guideline. Only cross-sectional and case-control studies that reported potential systemic biomarkers of periodontitis in peripheral immune cell types were included. DNA methylation was analyzed in leukocytes, and gene expression was in polymorphonuclear and mononuclear cells. Hypermethylation was found in TLR regulators genes: MAP3K7, MYD88, IL6R, RIPK2, FADD, IRAK1BP1, and PPARA in early stages of periodontitis, while advanced stages presented hypomethylation of these genes. TGFB1I1, VNN1, HLADRB4, and CXCL8 genes were differentially expressed in lymphocytes and monocytes of subjects with poorly controlled diabetes mellitus, dyslipidemia, and periodontitis in comparison with controls. The DAB2 gene was differentially overexpressed in periodontitis and dyslipidemia. Peripheral blood neutrophils in periodontitis showed differential expression in 163 genes. Periodontitis showed an increase in ceruloplasmin gene expression in polymorphonuclears in comparison with controls. Several genes highlight the role of the epigenetics of peripheral inflammatory cells in periodontitis that could be explored in blood as a source of biomarkers for routine testing. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Immunology in Chile)

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30 pages, 16251 KiB

Open AccessReview

Involvement of Inflammation and Its Resolution in Disease and Therapeutics

by Sebastián Alfaro, Vania Acuña, Ricardo Ceriani, María Fernanda Cavieres, Caroline Ruth Weinstein-Oppenheimer and Carolina Campos-Estrada

Int. J. Mol. Sci. 2022, 23(18), 10719; https://doi.org/10.3390/ijms231810719 - 14 Sep 2022

Cited by 14 | Viewed by 4548

Abstract

Inflammation plays a critical role in the response to and survival from injuries and/or infections. It occurs in two phases: initiation and resolution; however, when these events do not resolve and persist over time, the inflammatory response becomes chronic, prompting diseases that affect several systems and organs, such as the vasculature and the skin. Here, we reviewed inflammation that occurs in selected infectious and sterile pathologies. Thus, the immune processes induced by bacterial sepsis as well as T. cruzi and SARS-CoV-2 infections are shown. In addition, vaccine adjuvants as well as atherosclerosis are revised as examples of sterile-mediated inflammation. An example of the consequences of a lack of inflammation resolution is given through the revision of wound healing and chronic wounds. Then, we revised the resolution of the latter through advanced therapies represented by cell therapy and tissue engineering approaches, showing how they contribute to control chronic inflammation and therefore wound healing. Finally, new pharmacological insights into the management of chronic inflammation addressing the resolution of inflammation based on pro-resolving mediators, such as lipoxin, maresin, and resolvins, examining their biosynthesis, biological properties, and pharmacokinetic and pharmaceuticals limitations, are given. We conclude that resolution pharmacology and advanced therapies are promising tools to restore the inflammation homeostasis. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Immunology in Chile)

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19 pages, 2241 KiB

Open AccessReview

Senescent CD4⁺CD28⁻ T Lymphocytes as a Potential Driver of Th17/Treg Imbalance and Alveolar Bone Resorption during Periodontitis

by Luis González-Osuna, Alfredo Sierra-Cristancho, Emilio A. Cafferata, Samanta Melgar-Rodríguez, Carolina Rojas, Paola Carvajal, Cristian Cortez and Rolando Vernal

Int. J. Mol. Sci. 2022, 23(5), 2543; https://doi.org/10.3390/ijms23052543 - 25 Feb 2022

Cited by 8 | Viewed by 3391

Abstract

Senescent cells express a senescence-associated secretory phenotype (SASP) with a pro-inflammatory bias, which contributes to the chronicity of inflammation. During chronic inflammatory diseases, infiltrating CD4⁺ T lymphocytes can undergo cellular senescence and arrest the surface expression of CD28, have a response biased towards T-helper type-17 (Th17) of immunity, and show a remarkable ability to induce osteoclastogenesis. As a cellular counterpart, T regulatory lymphocytes (Tregs) can also undergo cellular senescence, and CD28⁻ Tregs are able to express an SASP secretome, thus severely altering their immunosuppressive capacities. During periodontitis, the persistent microbial challenge and chronic inflammation favor the induction of cellular senescence. Therefore, senescence of Th17 and Treg lymphocytes could contribute to Th17/Treg imbalance and favor the tooth-supporting alveolar bone loss characteristic of the disease. In the present review, we describe the concept of cellular senescence; particularly, the one produced during chronic inflammation and persistent microbial antigen challenge. In addition, we detail the different markers used to identify senescent cells, proposing those specific to senescent T lymphocytes that can be used for periodontal research purposes. Finally, we discuss the existing literature that allows us to suggest the potential pathogenic role of senescent CD4⁺CD28⁻ T lymphocytes in periodontitis. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Immunology in Chile)

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