COVID-19 Pandemic and Periodontal Practice: The Immunological, Clinical, and Economic Points of View.

The recent global health problem, COVID-19, has had far-reaching impacts on lifestyles. Although many effective WHO-approved vaccines have been produced that have reduced the spread and severity of the disease, it appears to persist in humans for a long time and possibly forever as everyday it turns out to have new mutations. COVID-19 involves the lungs and other organs primarily through cytokine storms, which have been implicated in many other inflammatory disorders, including periodontal diseases. COVID-19 is in a close association with dental and periodontal practice from two respects: first, repeated mandatory lockdowns have reduced patient referrals to dentists and limited the dental and periodontal procedures to emergency treatments, whereas it is important to recognize the oral manifestations of COVID-19 as well as the influence of oral and periodontal disease on the severity of COVID-19. Second, dentistry is one of the high-risk professions in terms of close contact with unmasked individuals, necessitating redefining the principles of infection control. The pressures of the economic recession on patients as well as dentists add to the difficulty of resuming elective dental services. Therefore, this study is divided into two parts corresponding to what mentioned above: the first part examines the clinical and immunological associations between COVID-19 and periodontal and oral diseases, and the second part delineates the measures needed to control the disease transmission in dental clinics as well as the economic impact of the pandemic era on dental services.

Crosstalk between Venous Thromboembolism and Periodontal Diseases: A Bioinformatics Analysis.

BACKGROUND: This current study applied bioinformatics analysis to reveal the crosstalk between venous thromboembolism (VTE) and periodontitis, as well as the potential role of immune-related genes in this context. METHODS: Expression data were downloaded from the GEO database. Blood samples from venous thromboembolism (VTE) were used (GSE19151), while for periodontal disease, we used gingival tissue samples (GSE10334, GSE16134, and GSE23586). After batch correction, we used "limma" packages of R language for differential expression analysis (p value < 0.05, ∣logFC | ≥0.5). We used Venn diagrams to extract the differentially expressed genes common to VTE and periodontitis as potential crosstalk genes and applied functional enrichment analysis (GO biological process and KEGG pathway). The protein-protein interaction (PPI) network of crosstalk genes was constructed by Cytoscape software. The immune-related genes were downloaded from the literature. The Wilcoxon test was used to test the scores of immune infiltrating cells. The crosstalk genes were further screened by LASSO Logistic Regression. RESULTS: For periodontitis, 427 case and 136 control samples, and for VTE, 70 case and 63 control samples were included. The obtained PPI network had 1879 nodes and 2257 edges. Moreover, 782 immune genes and 28 cell types were included in the analysis. Over 90% of immune cells had different expressions in VTE and periodontitis. We obtained 12 significant pathways corresponding to crosstalk genes. CD3D, CSF3R, and CXCR4 acted as an immune gene and a crosstalk gene. We obtained a total of 12 shared biomarker crosstalk genes. Among those 12 biomarker crosstalk genes, 4 were immune genes (LGALS1, LSP1, SAMSN1, and WIPF1). CONCLUSION: Four biomarker crosstalk genes between periodontitis and VTE were also immune genes, i.e., LGALS1, LSP1, SAMSN1, and WIPF1. The findings of the current study need further validation and are a basis for development of biomarkers.

Multifaceted Impacts of Periodontal Pathogens in Disorders of the Intestinal Barrier.

Periodontal disease, a common inflammatory disease, is considered a hazardous factor that contributes to the development of diseases of the digestive system as well as other systems. The bridge between periodontitis and systemic diseases is believed to be periodontal pathogens. The intestine, as part of the lower gastrointestinal tract, has a close connection with the oral cavity. Within the intestine, the intestinal barrier acts as a multifunctional system including microbial, mucous, physical and immune barrier. The intestinal barrier forms the body's first line of defense against external pathogens; its breakdown can lead to pathological changes in the gut and other organs or systems. Reports in the literature have described how oral periodontal pathogens and pathobiont-reactive immune cells can transmigrate to the intestinal mucosa, causing the destruction of intestinal barrier homeostasis. Such findings might lead to novel ideas for investigating the relationship between periodontal disease and other systemic diseases. This review summarizes studies on the effects of periodontal pathogens on the intestinal barrier, which might contribute to understanding the link between periodontitis and gastrointestinal diseases.

Identification of Periopathogens in Atheromatous Plaques Obtained from Carotid and Coronary Arteries.

Increasing attention has been paid to the possible link between periodontal disease and atherosclerosis over the past decade. The aim of this study is to investigate the presence of five periopathogens: Porphyromonas gingivalis (P.g.), Aggregatibacter actinomycetemcomitans (A.a.), Tannerella forsythia (T.f.), Treponema denticola (T.d.), and Prevotella intermedia (P.i.) in atheromatous plaques obtained from the carotid and coronary arteries in patients who underwent coronary artery bypass graft surgery and carotid endarterectomy. Group I (carotid arteries) consisted of 30 patients (mean age: 54.5 ± 14.8), and group II (coronary arteries) consisted of 28 patients (mean age: 63 ± 12.1). Clinical periodontal examinations consisted of plaque index, gingival index, sulcus bleeding index, and periodontal probing depth and were performed on the day of vascular surgery. The presence of periopathogens in periodontal pockets and atherosclerotic vessels was detected using polymerase chain reaction. In both subgingival plaque and atherosclerotic plaque of carotid arteries, P.g., A.a., T.f., T.d., and P.i. were detected in 26.7%, 6.7%, 66.7%, 10.0%, and 20.0%, respectively, while for coronary arteries, P.g. was detected in 39.3%, A.a. in 25%, T.f. in 46.4%, T.d. in 7.1%, and P.i. in 35.7%. The presence of five periopathogens in carotid and coronary atherosclerotic vessels showed correlation in regard to the degree of periodontal inflammation. The present study suggests the relationship between periodontal pathogenic bacteria and atherogenesis. Further studies are necessary in relation to the prevention or treatment of periodontal disease that would result in reduced mortality and morbidity associated with atherosclerosis.

Covid-19 and oral diseases: Crosstalk, synergy or association?

The coronavirus disease 2019 (Covid-19) is a viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that clinically affects multiple organs of the human body. Cells in the oral cavity express viral entry receptor angiotensin-converting enzyme 2 that allows viral replication and may cause tissue inflammation and destruction. Recent studies have reported that Covid-19 patients present oral manifestations with multiple clinical aspects. In this review, we aim to summarise main signs and symptoms of Covid-19 in the oral cavity, its possible association with oral diseases, and the plausible underlying mechanisms of hyperinflammation reflecting crosstalk between Covid-19 and oral diseases. Ulcers, blisters, necrotising gingivitis, opportunistic coinfections, salivary gland alterations, white and erythematous plaques and gustatory dysfunction were the most reported clinical oral manifestations in patients with Covid-19. In general, the lesions appear concomitant with the loss of smell and taste. Multiple reports show evidences of necrotic/ulcerative gingiva, oral blisters and hypergrowth of opportunistic oral pathogens. SARS-CoV-2 exhibits tropism for endothelial cells and Covid-19-mediated endotheliitis can not only promote inflammation in oral tissues but can also facilitate virus spread. In addition, elevated levels of proinflammatory mediators in patients with Covid-19 and oral infectious disease can impair tissue homeostasis and cause delayed disease resolution. This suggests potential crosstalk of immune-mediated pathways underlying pathogenesis. Interestingly, few reports suggest recurrent herpetic lesions and higher bacterial growth in Covid-19 subjects, indicating SARS-CoV-2 and oral virus/bacteria interaction. Larger cohort studies comparing SARS-CoV-2 negative and positive subjects will reveal oral manifestation of the virus on oral health and its role in exacerbating oral infection.

Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities.

Periodontitis, a major inflammatory disease of the oral mucosa, is epidemiologically associated with other chronic inflammation-driven disorders, including cardio-metabolic, neurodegenerative and autoimmune diseases and cancer. Emerging evidence from interventional studies indicates that local treatment of periodontitis ameliorates surrogate markers of comorbid conditions. The potential causal link between periodontitis and its comorbidities is further strengthened by recent experimental animal studies establishing biologically plausible and clinically consistent mechanisms whereby periodontitis could initiate or aggravate a comorbid condition. This multi-faceted 'mechanistic causality' aspect of the link between periodontitis and comorbidities is the focus of this Review. Understanding how certain extra-oral pathologies are affected by disseminated periodontal pathogens and periodontitis-associated systemic inflammation, including adaptation of bone marrow haematopoietic progenitors, may provide new therapeutic options to reduce the risk of periodontitis-associated comorbidities.

Porphyromonas gingivalis gingipains potentially affect MUC5AC gene expression and protein levels in respiratory epithelial cells.

Porphyromonas gingivalis (Pg) is a periodontopathic pathogen that may affect MUC5AC-related mucus hypersecretion along airway epithelial cells. Here, we attempted to establish whether Pg virulence factors (lipopolysaccharide, FimA fimbriae, gingipains) affect MUC5AC in immortalized and primary bronchial cells. We report that MUC5AC gene expression and protein levels are affected by Pg culture supernatant, but not by lipopolysaccharide or FimA fimbriae. Cells treated with either Pg single (Kgp or Rgp) or double (Kgp/Rgp) mutants had altered levels of MUC5AC gene expression and protein levels, and MUC5AC staining of double mutant-treated mouse lung cells showed that MUC5AC protein levels were unaffected. Taken together, we propose that Pg gingipains may be the primary virulence factor that influences both MUC5AC gene expression and protein levels.

Innate Phagocyte Polarization in the Oral Cavity.

The oral cavity is a complex environment constantly exposed to antigens from food and the oral microbiota. Innate immune cells play an essential role in maintaining health and homeostasis in the oral environment. However, these cells also play a significant role in disease progression. This review will focus on two innate phagocytes in the oral cavity: macrophages and neutrophils, and examine their roles during homeostasis and disease development, with a focus on periodontal disease and cancer. Macrophages have a well-known ability to polarize and be activated towards a variety of phenotypes. Several studies have found that macrophages' polarization changes can play an essential role in maintaining health in the oral cavity and contribute to disease. Recent data also finds that neutrophils display phenotypic heterogeneity in the oral cavity. In both cases, we focus on what is known about how these cellular changes alter these immune cells' interactions with the oral microbiota, including how such changes can lead to worsening, rather than improving, disease states.

The Oral Host-Microbial Interactome: An Ecological Chronometer of Health?

An increasing number of studies reveal that host-microbial interactome networks are coordinated, impacting human health and disease. Recently, several lines of evidence have revealed associations between the acquisition of a complex microbiota and adaptive immunity, supporting that host-microbiota symbiotic relationships have evolved as a means to maintain homeostasis where the role of the microbiota is to promote and educate the immune system. Here, we hypothesize an oral host-microbial interactome that could serve as an ecological chronometer of health and disease, with specific focus on caries, periodontal diseases, and cancer. We also review the current state of the art on the human oral microbiome and its correlations with host innate immunity, and host cytokine control, with the goal of using this information for disease prediction and designing novel treatments for local and systemic dysbiosis. In addition, we discuss new insights into the role of novel host-microbial signals as potential biomarkers, and their relevance for the future of precision dentistry and medicine.

Influence of Natural Killer Cells and Natural Killer T Cells on Periodontal Disease: A Systematic Review of the Current Literature.

Natural killer (NK) cells, as members of the innate immune system, and natural killer T (NKT) cells, bridging innate and adaptive immunity, play a prominent role in chronic inflammatory diseases and cancerogenesis, yet have scarcely been examined in oral diseases. Therefore, systematic research on the latest literature focusing on NK/NKT cell-mediated mechanisms in periodontal disease, including the time period 1988-2020, was carried out in MEDLINE (PubMed) using a predetermined search strategy, with a final selection of 25 studies. The results showed that NK cells tend to have rather proinflammatory influences via cytokine production, cytotoxic effects, dendritic-cell-crosstalk, and autoimmune reactions, while contrarily, NKT cell-mediated mechanisms were proinflammatory and immunoregulatory, ranging from protective effects via B-cell-regulation, specific antibody production, and the suppression of autoimmunity to destructive effects via cytokine production, dendritic-cell-crosstalk, and T-/B-cell interactions. Since NK cells seem to have a proinflammatory role in periodontitis, further research should focus on the proinflammatory and immunoregulatory properties of NKT cells in order to create, in addition to antibacterial strategies in dental inflammatory disease, novel anti-inflammatory therapeutic approaches modulating host immunity towards dental health.

Serum IgG titers against periodontal pathogens are associated with cerebral hemorrhage growth and 3-month outcome.

To assess the influence of periodontal disease on cerebral hemorrhage and its clinical course, we examined the association of the serum IgG titer of periodontal pathogens with hemorrhage growth and 3-month outcome. We consecutively enrolled 115 patients with acute cerebral hemorrhage (44 females, aged 71.3 ± 13.1 years) and used ELISA to evaluate the serum IgG titers of 9 periodontal pathogens: Porphyromonas gingivalis, Aggregatibacter (A.) actinomycetemcomitans, Prevotella intermedia, Prevotella nigrescens, Fusobacterium (F.) nucleatum, Treponema denticola, Tannerella forsythensis, Campylobacter rectus, and Eikenella corrodens. Significant hematoma growth was defined as an increase in the volume of >33% or an absolute increase in the volume of >12.5 mL. A poor outcome was defined as a 3 or higher on the modified Rankin Scale. We observed hemorrhage growth in 13 patients (11.3%). Multivariate analysis revealed that increased IgG titers of A. actinomycetemcomitans independently predicted the elevated hemorrhage growth (odds ratio 5.26, 95% confidence interval 1.52-18.25, p = 0.01). Notably, augmented IgG titers of F. nucleatum but not A. actinomycetemcomitans led to a poorer 3-month outcome (odds ratio 7.86, 95% confidence interval 1.08-57.08, p = 0.04). Thus, we demonstrate that elevated serum IgG titers of A. actinomycetemcomitans are an independent factor for predicting cerebral hemorrhage growth and that high serum IgG titers of F. nucleatum may predict a poor outcome in patients with this disease. Together, these novel data reveal how systemic periodontal pathogens may affect stroke patients, and, should, therefore, be taken into consideration in the management and treatment of these individuals.

AIM2 Inflammasome's First Decade of Discovery: Focus on Oral Diseases.

A common feature of many acute and chronic oral diseases is microbial-induced inflammation. Innate immune responses are the first line of defense against pathogenic microorganisms and are initiated by pattern recognition receptors (PRRs) that specifically recognize pathogen-associated molecular patterns and danger-associated molecular patterns. The activation of certain PRRs can lead to the assembly of macromolecular oligomers termed inflammasomes, which are responsible for pro-inflammatory cytokine maturation and secretion and thus activate host inflammatory responses. About 10 years ago, the absent in melanoma 2 (AIM2) was independently discovered by four research groups, and among the "canonical" inflammasomes [including AIM2, NLR family pyrin domain (NLRP)1, NLRP3, NLR family apoptosis inhibitory protein (NAIP)/NLR family, caspase activation and recruitment domain (CARD) containing (NLRC)4, and pyrin], AIM2 so far is the only one that simultaneously acts as a cytosolic DNA sensor due to its DNA-binding ability. Undoubtedly, such a double-faceted role gives AIM2 greater mission and more potential in the mediation of innate immune responses. Therefore, AIM2 has garnered much attention from the broad scientific community during its first 10 years of discovery (2009-2019). How the AIM2 inflammasome is related to oral diseases has aroused debate over the past few years and is under active investigation. AIM2 inflammasome may potentially be a key link between oral diseases and innate immunity. In this review, we highlight the current knowledge of the AIM2 inflammasome and its critical role in the pathogenesis of various oral diseases, which might offer future possibilities for disease prevention and targeted therapy utilizing this continued understanding.

Poor Oral Hygiene and High Levels of Inflammatory Cytokines in Saliva Predict the Risk of Overweight and Obesity.

The study aimed to determine if oral hygiene influences not only oral health but also potentially metabolic disorders such as overweight or obesity. Participants were 94 patients: 40 with increased body mass and 54 with normal body mass. The methods included dental examination, a questionnaire concerning hygienic habits and an assessment of selected salivary inflammatory markers. The new parameter named "cleaning index" (describing the interaction between average time of tooth brushing in minutes and its frequency per day) significantly correlated with Body Mass Index (RSpearman = 0.300). The multivariate regression model incorporating cleaning index, approximal plaque index, receptor 1 for tumor necrosis factor-alpha (TNFα-R1) and interleukin-15 (IL-15) had a high power to predict overweight or obesity (AUC = 0.894). Patients with poor oral hygiene (approximal plaque index >40%) were more than eight times more likely to suffer from obesity than patients with good oral hygiene. Cleaning index higher than 4 decreased the odds by about 85%. Oral hygiene habits, adjusted by salivary concentrations of selected inflammatory markers may allow predicting effectively overweight or obesity risk. Early proper dental prophylaxis and treatment could lead to the better prevention of metabolic disorders.

Clinical Applications of Interleukin-37: A Key Player in the Immunopathogenesis of Immune Disorders.

Recently, the era of medicine has been encountered with the exponential growth of special seroimmunobiomarkers in clinical trials. Lately, Interleukin-37 (IL-37) has attracted a wide range of basic medical scientists' attention due to its controversial functions in physiologic or pathologic microenvironments. In this research, an updated overview of immunobiological functions and clinical applications of IL-37 in a wide range of diseases, are discussed in order to highlight the role of recent laboratory-based results of IL-37. Data of this systematic review article were collected from initial 237 articles in Google Scholar search engine, Science Direct, PubMed, Scopus, and Embase databases. Eventually, 134 total articles were considered from March 2000 to June 2019 time interval, by using 5 keywords. Relevant English articles, abstracts and conference papers all were included. No restrictions of methods and type of the article were imposed. As one of the newly immunotherapeutic based approaches, clinical applications of cytokines are promisingly taken into account for diagnosis and treatment of multiple diseases. Various evidence suggests that IL-37 has notable roles in the regulation of acute and chronic inflammatory responses. Also, IL-37 has been studied in pregnancy, obesity, infectious, cardiovascular, neurologic, autoimmune, and metabolic diseases. Also, the protective functions of IL-37 against multiple cancers, are disputably related to the type and stage of cancer as well as the IL-37 variant. The broad spectrum of IL-37 and its receptors in diseases, seem to be a potential candidate with pivotal effects for immunomodulation and immune gene therapy of various pathologic states.

Evaluation of Endocan and Tumor Necrosis Factor-α as Inflammatory Biomarkers in Type 2 Diabetes and Periodontal Disease.

Purpose: Type 2 diabetes mellitus (type 2 DM) and periodontitis encompass vascular endothelial changes. Endocan, a marker of endothelial dysfunction, has not been previously evaluated in diabetic patients with periodontal disease. This study was designed to evaluate the levels of endocan and tumor necrosis factor-alpha (TNF-α) in chronic periodontitis (CP) subjects with type 2 DM before and after nonsurgical periodontal therapy (NSPT). Materials and Methods: This study included 75 subjects with varying degrees of CP. Group I-included 25 systemically healthy individuals with CP, and Groups II and III-included 25 CP patients each with type 2 DM under good control (hemoglobin A1c [HbA1c] <7%) and poor control (HbA1c >8%), respectively. Periodontal parameters were assessed, and gingival crevicular fluid collections were performed for all patients at baseline and again following three months of NSPT. Levels of endocan and TNF-α were assessed using enzyme-linked immunosorbent assay. Results: Endocan levels were elevated in CP subjects with type 2 DM at baseline. There was a significant reduction in the Endocan and HbA1c levels (p < 0.01) among all the groups after NSPT. Conclusion: Endocan may be used as a novel diagnostic marker for pateints with type 2 DM and CP and as a potential prognostic marker for monitoring improvement in periodontal and glycemic status during NSPT.

The intriguing commonality of NETosis between COVID-19 & Periodontal disease.

NETosis, being an alternative form of cell death is the creation of web-like chromatin decondensates by suitably primed neutrophils as a response to stimulus aimed at containing and eliminating the same. In certain situations, it causes more harm than benefit in the form of bystander damage directly or via activation of autoimmune mechanisms. Such pathophysiology finds evidence in both Periodontal disease and COVID-19. Coupled with impaired removal, NETs have been implicated in both these disease forms to promote a state of inflammation and be a source of constant harm to the tissues involved. This potentially forms groundwork to implicate Periodontal disease as predisposing towards adverse COVID-19 related outcomes.

An Evidence-Based Update on the Molecular Mechanisms Underlying Periodontal Diseases.

Several investigators have reported about the intricate molecular mechanism underlying periodontal diseases (PD). Nevertheless, the role of specific genes, cells, or cellular mechanisms involved in the pathogenesis of periodontitis are still unclear. Although periodontitis is one of the most prevalent oral diseases globally, there are no pre-diagnostic markers or therapeutic targets available for such inflammatory lesions. A pivotal role is played by pro- and anti-inflammatory markers in modulating pathophysiological and physiological processes in repairing damaged tissues. In addition, effects on osteoimmunology is ever evolving due to the ongoing research in understanding the molecular mechanism lying beneath periodontal diseases. The aim of the current review is to deliver an evidence-based update on the molecular mechanism of periodontitis with a particular focus on recent developments. Reports regarding the molecular mechanism of these diseases have revealed unforeseen results indicative of the fact that significant advances have been made to the periodontal medicine over the past decade. There is integrated hypothesis-driven research going on. Although a wide picture of association of periodontal diseases with immune response has been further clarified with present ongoing research, small parts of the puzzle remain a mystery and require further investigations.

Polymicrobial periodontal disease triggers a wide radius of effect and unique virome.

Periodontal disease is a microbially-mediated inflammatory disease of tooth-supporting tissues that leads to bone and tissue loss around teeth. Although bacterially-mediated mechanisms of alveolar bone destruction have been widely studied, the effects of a polymicrobial infection on the periodontal ligament and microbiome/virome have not been well explored. Therefore, the current investigation introduced a new mouse model of periodontal disease to examine the effects of a polymicrobial infection on periodontal ligament (PDL) properties, changes in bone loss, the host immune response, and the microbiome/virome using shotgun sequencing. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, and Fusobacterium nucleatum were used as the polymicrobial oral inoculum in BALB/cByJ mice. The polymicrobial infection triggered significant alveolar bone loss, a heightened antibody response, an elevated cytokine immune response, a significant shift in viral diversity and virome composition, and a widening of the PDL space; the latter two findings have not been previously reported in periodontal disease models. Changes in the PDL space were present at sites far away from the site of insult, indicating that the polymicrobial radius of effect extends beyond the bone loss areas and site of initial infection and wider than previously appreciated. Associations were found between bone loss, specific viral and bacterial species, immune genes, and PDL space changes. These findings may have significant implications for the pathogenesis of periodontal disease and biomechanical properties of the periodontium. This new polymicrobial mouse model of periodontal disease in a common mouse strain is useful for evaluating the features of periodontal disease.

Resident memory T cells: Possible players in periodontal disease recurrence.

BACKGROUND/OBJECTIVES: Tissue-resident memory T cells (Trm) represent a new subset of long-lived memory T cells that remain in barrier tissues after previous bacterial or viral infection to support early/immediate defense mechanisms, providing site-specific protection from pathogen challenge. As data on Trm cells in human gingiva are just emerging, the aim of the present study was to explore their presence and distribution in epithelial and connective periodontal tissues in relation to microbial exposure and periodontal damage. MATERIAL AND METHODS: Periodontitis tissue specimens were collected from 20 generalized chronic periodontitis patients at the time of osseous resective surgery. As a control, 18 healthy tissue specimens were harvested each from both the primary flap and the palatal graft in 18 periodontally healthy patients during mucogingival surgeries. As CD69 and CD103 are phenotypic markers associated with tissue residence, intraepithelial and stromal CD103+ and CD69+ cells per high-power field were counted in areas with highest expression. Double immunohistochemistry for CD3 and CD69 was performed to identify T cells. RESULTS: CD69 +and CD103+ cells showed a lymphocytic morphology, and double CD69 and CD3 staining confirmed the T cell phenotype of these cells. CD103 and CD69 expression was significantly enhanced in epithelial and connective tissues from patients with periodontitis compared with healthy controls (P < .001). Significant positive correlation between PD and both CD103 and CD69 epithelial expression was observed in tissue specimens from periodontitis patients (P < .001). CONCLUSION: Within the limits of the present study, these results indicate that Trm cells are higher in periodontitis lesions. They could orchestrate the host response to microbial challenge, leading to a faster reactivation of periodontal disease.

Stressed-Out Oral Immunity: A Gateway From Socioeconomic Adversity to Periodontal Disease.

OBJECTIVE: It has been suggested that adverse socioeconomic conditions "get under the skin" by eliciting a stress response that can trigger periodontal inflammation. We aimed to a) estimate the extent to which socioeconomic position (SEP) is associated with periodontal disease (PD) and proinflammatory oral immunity, and b) determine the contribution of psychosocial stress and stress hormones to these relationships. METHODS: In this cross-sectional study (n = 102), participants (20-59 years old) completed financial and perceived stress questionnaires and underwent full-mouth periodontal examinations. SEP was characterized by annual household income and educational attainment. Cortisol, a biological correlate of chronic stress, was assessed in hair samples. Oral immunity was characterized by assessing oral inflammatory load and proinflammatory oral neutrophil function. Blockwise Poisson and logistic regression models were applied. RESULTS: Compared with lower SEP, individuals in the middle- and higher-income categories had a significantly lower probability of PD (incidence rate ratio [IRR] = 0.5 [confidence interval {CI} = 0.3-0.7] and IRR = 0.4 [95% CI = 0.2-0.7]) and oral inflammatory load (IRR = 0.6 [95% CI = 0.3-0.8] and IRR = 0.5 [95% CI = 0.3-0.7]) and were less likely to have a proinflammatory oral immune function (odds ratio [OR] = 0.1 [95% CI = 0.0-0.7] and OR = 0.1 [95% CI = 0.0-0.9]). PD and oral immune parameters were significantly associated with financial stress and cortisol. Adjusting for financial stress and cortisol partially attenuated the socioeconomic differences in PD to IRR = 0.7 (95% CI = 0.5-0.8) and IRR = 0.6 (95% CI = 0.5-0.7) for the middle- and higher-income categories, respectively. Similar results were observed for proinflammatory immunity (OR = 0.2 [95% CI = 0.0-1.8] and OR = 0.3 [95% CI = 0.0-2.3]). CONCLUSION: These findings suggest that psychosocial stress may contribute to a proinflammatory immunity that is implicated in PD pathobiology and provide insight into social-to-biological processes in oral health.