Eosinophils in Oral Disease: A Narrative Review.

The prevalence of diseases characterised by eosinophilia is on the rise, emphasising the importance of understanding the role of eosinophils in these conditions. Eosinophils are a subset of granulocytes that contribute to the body's defence against bacterial, viral, and parasitic infections, but they are also implicated in haemostatic processes, including immunoregulation and allergic reactions. They contain cytoplasmic granules which can be selectively mobilised and secrete specific proteins, including chemokines, cytokines, enzymes, extracellular matrix, and growth factors. There are multiple biological and emerging functions of these specialised immune cells, including cancer surveillance, tissue remodelling and development. Several oral diseases, including oral cancer, are associated with either tissue or blood eosinophilia; however, their exact mechanism of action in the pathogenesis of these diseases remains unclear. This review presents a comprehensive synopsis of the most recent literature for both clinicians and scientists in relation to eosinophils and oral diseases and reveals a significant knowledge gap in this area of research.

γδ T cells in oral diseases.

OBJECTIVE: γδ T cells are a distinct subset of unconventional T cells, which link innate and adaptive immunity by secreting cytokines and interacting with other immune cells, thereby modulating immune responses. As the first line of host defense, γδ T cells are essential for mucosal homeostasis and immune surveillance. When abnormally activated or impaired, γδ T cells can contribute to pathogenic processes. Accumulating evidence has revealed substantial impacts of γδ T cells on the pathogenesis of cancers, infections, and immune-inflammatory diseases. γδ T cells exhibit dual roles in cancers, promoting or inhibiting tumor growth, depending on their phenotypes and the clinical stage of cancers. During infections, γδ T cells exert high cytotoxic activity in infectious diseases, which is essential for combating bacterial and viral infections by recognizing foreign antigens and activating other immune cells. γδ T cells are also implicated in the onset and progression of immune-inflammatory diseases. However, the specific involvement and underlying mechanisms of γδ T cells in oral diseases have not been systematically discussed. METHODS: We conducted a systematic literature review using the PubMed/MEDLINE databases to identify and analyze relevant literature on the roles of γδ T cells in oral diseases. RESULTS: The literature review revealed that γδ T cells play a pivotal role in maintaining oral mucosal homeostasis and are involved in the pathogenesis of oral cancers, periodontal diseases, graft-versus-host disease (GVHD), oral lichen planus (OLP), and oral candidiasis. γδ T cells mainly influence various pathophysiological processes, such as anti-tumor activity, eradication of infection, and immune response regulation. CONCLUSION: This review focuses on the involvement of γδ T cells in oral diseases, with a particular emphasis on the main functions and underlying mechanisms by which γδ T cells influence the pathogenesis and progression of these conditions. This review underscores the potential of γδ T cells as therapeutic targets in managing oral health issues.

Implications of innate lymphoid cells in oral diseases.

Innate lymphoid cells (ILCs), as newly discovered antigen-independent innate immune cells, respond promptly to stimuli by secreting effector cytokines to exert effector functions similar to those of T cells. ILCs predominantly reside at mucosal sites and play critical roles in defending against infections, maintaining mucosal homeostasis, regulating inflammatory and immune responses, and participating in tumorigenesis. Recently, there has been a growing interest in the role of ILCs in oral diseases. This review outlines the classifications and the major characteristics of ILCs, and then comprehensively expatiates the research on ILCs in oral cancer, primary Sjogren's syndrome, periodontal diseases, oral lichen planus, oral candidiasis, Behcet's disease, and pemphigus vulgaris, aiming at summarising the implications of ILCs in oral diseases and providing new ideas for further research.

The human microbiome in immunobullous disorders and lichen planus.

For several decades, there has been a significant growth in the incidence of autoimmune diseases. Studies indicate that genetic factors may not be the only trigger for disease development and that dysbiosis of the microbiome may be another mechanism involved in the pathogenesis of autoimmune diseases. The role of the microbiome in the development of common skin disorders such as psoriasis, atopic dermatitis, acne and rosacea is increasingly well understood. However, few studies have focused on lichen planus and the rare acquired immunobullous diseases, both mucocutaneous groups of disorders linked to skin, oral and gut microbiomes. This review provides an insight into the current understanding of how the microbiome may contribute to the development of autoimmunity and to the maintenance and exacerbation of acquired immunobullous and lichenoid diseases. These mechanisms may have implications for future preventive and therapeutic approaches.

PANoptosis: A New Insight Into Oral Infectious Diseases.

The oral microbiome, one of the most complex and intensive microbial ecosystems in the human body, comprises bacteria, archaea, fungi, protozoa, and viruses. Dysbiosis of the oral microbiome is the initiating factor that leads to oral infectious diseases. Infection is a sophisticated biological process involving interplay between the pathogen and the host, which often leads to activation of programmed cell death. Studies suggest that pyroptosis, apoptosis, and necroptosis are involved in multiple oral infectious diseases. Further understanding of crosstalk between cell death pathways has led to pyroptosis, apoptosis, and necroptosis being integrated into a single term: PANoptosis. PANoptosis is a multifaceted agent of the immune response that has important pathophysiological relevance to infectious diseases, autoimmunity, and cancer. As such, it plays an important role in innate immune cells that detect and eliminate intracellular pathogens. In addition to the classical model of influenza virus-infected and Yersinia-infected macrophages, other studies have expanded the scope of PANoptosis to include other microorganisms, as well as potential roles in cell types other than macrophages. In this review, we will summarize the pathophysiological mechanisms underlying inflammation and tissue destruction caused by oral pathogens. We present an overview of different pathogens that may induce activation of PANoptosis, along with the functional consequences of PANoptosis in the context of oral infectious diseases. To advance our understanding of immunology, we also explore the strategies used by microbes that enable immune evasion and replication within host cells. Improved understanding of the interplay between the host and pathogen through PANoptosis will direct development of therapeutic strategies that target oral infectious diseases.

"Oral Manifestations of Patients with Inherited Defect in Phagocyte Number or Function" a systematic review.

INTRODUCTION: Inherited phagocyte defects are one of the subgroups of primary immunodeficiency diseases (PIDs) with various clinical manifestations. As oral manifestations are common at the early ages, oral practitioners can have a special role in the early diagnosis. MATERIALS AND METHODS: A comprehensive search was conducted in this systematic review study and data of included studies were categorized into four subgroups of phagocyte defects, including congenital neutropenia, defects of motility, defects of respiratory burst, and other non-lymphoid defects. RESULTS: Among all phagocyte defects, 12 disorders had reported data for oral manifestations in published articles. A total of 987 cases were included in this study. Periodontitis is one of the most common oral manifestations. CONCLUSION: There is a need to organize better collaboration between medical doctors and dentists to diagnose and treat patients with phagocyte defects. Regular dental visits and professional oral health care are recommended from the time of the first primary teeth eruption in newborns.

Towards better understanding of giant cell granulomas of the oral cavity.

Giant cell granulomas are enigmatic lesions of the oral cavity characterised by a peculiar combined proliferation of mononuclear and multinucleated giant cells in a mesenchymal stromal background. Central and peripheral giant cell granulomas may have similar pathogenesis and histology but differ in their location and biological behaviour. It is important to differentiate them from other giant cell lesions that can occur in the oral cavity, such as giant cell tumour of the bone, aneurysmal bone cyst, brown tumour of hyperparathyroidism, and giant cell lesions of Ramon syndrome, Noonan syndrome, neurofibromatosis and Jaffe-Campanacci syndrome. A recent insight into their molecular genetics and pathogenesis, with identification of KRAS, FGFR1 and TRPV4 mutations, allows for better diagnostic differentiation and opens the door to the use of pathway inhibitors in the treatment of recurrent or dysmorphic lesions. In this review, we provide an updated summary of the clinical and pathological features of oral cavity giant cell granulomas that help with their precise diagnosis and management.

Pulmonary insults exacerbate susceptibility to oral Listeria monocytogenes infection through the production of IL-10 by NK cells.

Most individuals who consume foods contaminated with the bacterial pathogen Listeria monocytogenes (Lm) develop mild symptoms, while others are susceptible to life-threatening systemic infections (listeriosis). Although it is known that the risk of severe disease is increased in certain human populations, including the elderly, it remains unclear why others who consume contaminated food develop listeriosis. Here, we used a murine model to discover that pulmonary coinfections can impair the host's ability to adequately control and eradicate systemic Lm that cross from the intestines to the bloodstream. We found that the resistance of mice to oral Lm infection was dramatically reduced by coinfection with Streptococcus pneumoniae (Spn), a bacterium that colonizes the respiratory tract and can also cause severe infections in the elderly. Exposure to Spn or microbial products, including a recombinant Lm protein (L1S) and lipopolysaccharide (LPS), rendered otherwise resistant hosts susceptible to severe systemic Lm infection. In addition, we show that this increase in susceptibility was dependent on an increase in the production of interleukin-10 (IL-10) from Ncr1+ cells, including natural killer (NK) cells. Lastly, the ability of Ncr1+ cell derived IL-10 to increase disease susceptibility correlated with a dampening of both myeloid cell accumulation and myeloid cell phagocytic capacity in infected tissues. These data suggest that efforts to minimize inflammation in response to an insult at the respiratory mucosa render the host more susceptible to infections by Lm and possibly other pathogens that access the oral mucosa.

Amígdalas y adenoides: defensa ante agentes patógenos y su implicancia estomatológica / Tonsils and adenoids: defend to pathogenic agents and their stomatological involvement

La función de las amígdalas siempre ha sido discutida, desde afirmar que no tenían funcionalidad, hasta la actualidad que se plantea un papel inmunológico, con actividad linfocitaria de defensa, debido a la localización de linfocitos en el tejido de las amígdalas. Este artículo de actualización pretende describir desde la embriología, histología, fisiología, patología y estomatología, el rol que desempeñan las mismas en su papel inmunológico ante la acción de agentes patógenos. Se destaca la acción conjunta de las amígdalas palatinas, amígdalas faríngeas o adenoides, amígdalas peritubarias, amígdalas linguales y todo el resto de tejido linfático que conforman el anillo linfático faríngeo o anillo de Waldeyer, ya que cumplen un rol determinante en la defensa del organismo (AU)

The function of the tonsils has always been debated, from stating that they had no functionality, to the present day that an immunological role is proposed, with lymphocyte defense activity, due to the location of lymphocytes in the tissue of the tonsils. This update article aims to describe from embryology, histology, physiology, pathology and stomatology, the role they play in their immunological role against the action of pathogens. The joint action of the palatine tonsils, pharyngeal or adenoid tonsils, peritubal tonsils, lingual tonsils and all the rest of the lymphatic tissue that make up the pharyngeal lymphatic ring or Waldeyer's ring is highlighted, since they play a decisive role in the defense of the organism (AU)

Coexistence of Lack of Clinical Manifestation of Oral Mycosis and Systemic Diseases in Edentulous Patients Using Removable Prosthetic Restorations.

OBJECTIVE: It is believed that oral infections can increase the risk of systematic diseases, such as atherosclerosis and coronary heart disease, stroke, chronic obstructive pulmonary disease, diabetes, cancer, rheumatoid arthritis, etc. It seems that oral invasive pathogens induce a systemic inflammatory response via mediators released by the cardiovascular system and liver, which increases the risk to the patient of these systematic infections, such as hypertension. On the basis of previous studies of the stomatognathic system, investigating the coexistence of systemic diseases and inflammation in the oral cavity, it can be expected that there is a connection between inflammation of the denture-bearing area in patients using acrylic removable dentures and the presence of systemic diseases, and that patients with inflammation in oral mucosa are more likely to have systemic diseases. MATERIAL AND METHOD: A retrospective study was carried out on a group of patients seeking prosthetic treatment at the Prosthetic Department of the University Dental Clinic (UKS) from March 2012 to February 2013. All data were collected using a UKS electronic database with KS-SOMED. The minimum period of use for removable prostheses was five years. RESULTS: According to anamnesis, the most common systemic diseases in our study group were hypertension disease. In total, 58% of patients with hypertension disease had no inflammation in the oral cavity. CONCLUSIONS: The occurrence of systemic diseases in edentulous people using removable prosthetic restorations, and the subsequent use of medications for these diseases, may result in a lack of clinical symptoms of concomitant fungal infection of the oral mucosa.

Acute Oral Lesions.

A variety of acute oral lesions may be encountered in the scope of dermatology. Oral lesions may be single or multiple; may arise secondary to infectious, immune, congenital, medication use, or idiopathic causes; and may take a variety of forms. A thorough evaluation of the oral cavity is required to assess patients with oral lesions. Affected patients may be monitored, treated, or referred to an appropriate specialist for further management as needed. Many acute oral lesions are self-limiting in nature and patients may require only assessment and reassurance. Several common acute oral lesions are discussed in this article.

Chronic Oral Lesions.

Chronic oral mucosal lesions can be associated with several mucocutaneous diseases. This article reviews the autoimmune and immune-mediated, reactive, genetic, and infectious diseases that may present with chronic oral and/or cutaneous manifestations and provides a rational approach to diagnosis and management.

Oral Hypersensitivity Reactions.

Allergic contact hypersensitivity reactions of the oral mucosa pose a significant medical concern for some patients. Oral hypersensitivity reactions can result from a vast number of allergenic chemicals, but occur commonly from dental materials, flavorings, and preservatives. Clinical presentation is varied and often overlaps with other oral conditions, complicating their diagnosis and management. The most common clinical entities associated with oral hypersensitivity reactions are oral lichenoid reactions and allergic contact cheilitis. In addition to reviewing these conditions and their most common corresponding allergens, this article summarizes the pathogenesis of oral hypersensitivity reactions and addresses patch testing pearls.

An IL-17F.S65L Knock-In Mouse Reveals Similarities and Differences in IL-17F Function in Oral Candidiasis: A New Tool to Understand IL-17F.

Oropharyngeal candidiasis (OPC) is an opportunistic infection of the oral mucosa caused by the commensal fungus Candida albicans IL-17R signaling is essential to prevent OPC in mice and humans, but the individual roles of its ligands, IL-17A, IL-17F, and IL-17AF, are less clear. A homozygous IL-17F deficiency in mice does not cause OPC susceptibility, whereas mice lacking IL-17A are moderately susceptible. In humans, a rare heterozygous mutation in IL-17F (IL-17F.S65L) was identified that causes chronic mucocutaneous candidiasis, suggesting the existence of essential antifungal pathways mediated by IL-17F and/or IL-17AF. To investigate the role of IL-17F and IL-17AF in more detail, we exploited this "experiment of nature" by creating a mouse line bearing the homologous mutation in IL-17F (Ser65Leu) by CRISPR/Cas9. Unlike Il17f-/- mice that are resistant to OPC, Il17fS65L/S65L mice showed increased oral fungal burdens similar to Il17a -/- mice. In contrast to humans, however, disease was only evident in homozygous, not heterozygous, mutant mice. The mutation was linked to modestly impaired CXC chemokine expression and neutrophil recruitment to the infected tongue but not to alterations in oral antimicrobial peptide expression. These findings suggest mechanisms by which the enigmatic cytokine IL-17F contributes to host defense against fungi. Moreover, because these mice do not phenocopy Il17f-/- mice, they may provide a valuable tool to interrogate IL-17F and IL-17AF function in vivo in other settings.

Primary Immunodeficiencies With Defects in Innate Immunity: Focus on Orofacial Manifestations.

The field of primary immunodeficiencies (PIDs) is rapidly evolving. Indeed, the number of described diseases is constantly increasing thanks to the rapid identification of novel genetic defects by next-generation sequencing. PIDs are now rather referred to as "inborn errors of immunity" due to the association between a wide range of immune dysregulation-related clinical features and the "prototypic" increased infection susceptibility. The phenotypic spectrum of PIDs is therefore very large and includes several orofacial features. However, the latter are often overshadowed by severe systemic manifestations and remain underdiagnosed. Patients with impaired innate immunity are predisposed to a variety of oral manifestations including oral infections (e.g., candidiasis, herpes gingivostomatitis), aphthous ulcers, and severe periodontal diseases. Although less frequently, they can also show orofacial developmental abnormalities. Oral lesions can even represent the main clinical manifestation of some PIDs or be inaugural, being therefore one of the first features indicating the existence of an underlying immune defect. The aim of this review is to describe the orofacial features associated with the different PIDs of innate immunity based on the new 2019 classification from the International Union of Immunological Societies (IUIS) expert committee. This review highlights the important role played by the dentist, in close collaboration with the multidisciplinary medical team, in the management and the diagnostic of these conditions.

Regulation of host-microbe interactions at oral mucosal barriers by type 17 immunity.

The oral mucosa is a primary barrier site and a portal for entry of microbes, food, and airborne particles into the gastrointestinal tract. Nonetheless, mucosal immunity at this barrier remains understudied compared with other anatomical barrier sites. Here, we review basic aspects of oral mucosal histology, the oral microbiome, and common and clinically significant diseases that present at oral mucosal barriers. We particularly focus on the role of interleukin-17 (IL-17)/T helper 17 (TH17) responses in protective immunity and inflammation in the oral mucosa. IL-17/TH17 responses are highly relevant to maintaining barrier integrity and preventing pathogenic infections by the oral commensal fungus Candida albicans On the other hand, aberrant IL-17/TH17 responses are implicated in driving the pathogenesis of periodontitis and consequent bone and tooth loss. We discuss distinct IL-17-secreting T cell subsets, emphasizing their regulation and function in oropharyngeal candidiasis and periodontitis.

Oral manifestations of allograft recipients immediately before and after kidney transplantation.

Objective: To identify the oral lesions of individuals with kidney disease immediately before and shortly after kidney transplantation, taking into account the immunosuppressive regimen, antiviral prophylaxis and type of transplantation.Methods: A prospective observational cohort study was carried from January 2017 to January 2018. Eighty individuals aged 18 years or older who were admitted for kidney transplantation were eligible to participate. Clinical data regarding medical history, immunosuppressive therapy, antiviral prophylaxis, laboratorial data and oral examination were performed by the same trained researcher, in three different moments: 24 hours before transplantation (1st time point), 15-20 days (2nd time point) and 45-60 days (3rd time point) after transplantation.Results: In the first, second and third time points, it was found that 3.7% (3/80), 23.7% (18/76) and 25.7% (19/74) of the participants showed oral soft tissue lesions. Ulcers and candidiasis were the most frequent oral lesions, and they were associated with the use of everolimus (p = .005) and azathioprine (p = .034), respectively. Less patients reported xerostomia after transplantation than before (p < .001).Conclusions: Oral lesions are common in the short term after renal transplantation and are particularly related to both toxicities of immunosuppressive drugs and immunosuppression.