RESUMEN
The periodontal ligament (PDL) is a complex connective tissue that connects the tooth root to the dental alveolar bone and plays crucial mechanical roles. PDL also exhibits regenerative roles and regulatory functions to maintain periodontium integrity and homeostasis. While PDL exposure to oral microbial pathogens is common, virtually nothing is known regarding viral infections of PDL. In particular, human herpes simplex virus type 1 (HSV-1) persistently infects the oral cavity through infections of the oral epithelium, connective tissue and neurons. While the oral spread of HSV-1 is generally asymptomatic, this virus has also been implicated in various oral pathologies. In this study, using a primary cell model derived from PDL (PDL cells), and whole surgical fragments of PDL, we provide evidence supporting the efficient infection of PDL by HSV-1 and the promotion of cytopathic effects. Infection of PDL by HSV-1 was also associated with an acute innate inflammatory response, as illustrated by the production of antiviral interferons and pro-inflammatory cytokines. Furthermore, this inflammatory response to HSV-1 was exacerbated in the presence of bacterial-derived products, such as peptidoglycans. This work therefore highlights the ability of HSV-1 to infect mesenchymal cells from PDL, suggesting that PDL may serve as a viral reservoir for the periodontal spread of HSV-1. Moreover, this raises questions about HSV-1 oral pathogenesis, as HSV-1-associated cytopathic and inflammatory effects may contribute to profound alterations of PDL integrity and functioning.
Asunto(s)
Herpes Simple , Herpesvirus Humano 1 , Ligamento Periodontal , Humanos , Ligamento Periodontal/virología , Herpesvirus Humano 1/fisiología , Herpesvirus Humano 1/patogenicidad , Herpes Simple/virología , Citocinas/metabolismo , Células CultivadasRESUMEN
The oral cavity contributes to overall health, psychosocial well-being and quality of human life. Oral inflammatory diseases represent a major global health problem with significant social and economic impact. The development of effective therapies, therefore, requires deeper insights into the etiopathogenesis of oral diseases. Epstein-Barr virus (EBV) infection results in a life-long persistence of the virus in the host and has been associated with numerous oral inflammatory diseases including oral lichen planus (OLP), periodontal disease and Sjogren's syndrome (SS). There is considerable evidence that the EBV infection is a strong risk factor for the development and progression of these conditions, but is EBV a true pathogen? This long-standing EBV paradox yet needs to be solved. This review discusses novel viral aspects of the etiopathogenesis of non-tumorigenic diseases in the oral cavity, in particular, the contribution of EBV in OLP, periodontitis and SS, the tropism of EBV infection, the major players involved in the etiopathogenic mechanisms and emerging contribution of EBV-pathogenic bacteria bidirectional interaction. It also proposes the involvement of EBV-infected plasma cells in the development and progression of oral inflammatory diseases. A new direction for preventing and treating these conditions may focus on controlling pathogenic EBV with anti-herpetic drugs.
Asunto(s)
Antivirales/uso terapéutico , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4/inmunología , Enfermedades de la Boca , Animales , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/microbiología , Infecciones por Virus de Epstein-Barr/patología , Humanos , Enfermedades de la Boca/tratamiento farmacológico , Enfermedades de la Boca/inmunología , Enfermedades de la Boca/microbiología , Enfermedades de la Boca/virologíaRESUMEN
SLC5A8 is a sodium-coupled monocarboxylate and ketone transporter expressed in various epithelial cells. A putative role of SLC5A8 in neuroenergetics has been also hypothesized. To clarify this issue, we studied the cerebral phenotype of SLC5A8-deficient mice during aging. Elderly SLC5A8-deficient mice presented diffuse leukoencephalopathy characterized by intramyelinic oedema without demyelination suggesting chronic energetic crisis. Hypo-metabolism in the white matter of elderly SLC5A8-deficient mice was found using 99mTc-hexamethylpropyleneamine oxime (HMPAO) single-photon emission CT (SPECT). Since the SLC5A8 protein could not be detected in the mouse brain, it was hypothesized that the leukoencephalopathy of aging SLC5A8-deficient mice was caused by the absence of slc5a8 expression in a peripheral organ, i.e. the kidney, where SLC5A8 is strongly expressed. A hyper-excretion of the ketone ß-hydroxybutyrate (BHB) in the urine of SLC5A8-deficient mice was observed and showed that SLC5A8-deficient mice suffered a cerebral BHB insufficiency. Elderly SLC5A8-deficient mice also presented altered glucose metabolism. We propose that the continuous renal loss of BHB leads to a chronic energetic deficiency in the brain of elderly SLC5A8-deficient mice who are unable to counterbalance their glucose deficit. This study highlights the importance of alternative energetic substrates in neuroenergetics especially under conditions of restricted glucose availability.
Asunto(s)
Envejecimiento/metabolismo , Cuerpos Cetónicos/orina , Riñón/metabolismo , Leucoencefalopatías/metabolismo , Transportadores de Ácidos Monocarboxílicos/deficiencia , Sustancia Blanca/metabolismo , Ácido 3-Hidroxibutírico/orina , Envejecimiento/orina , Animales , Glucosa/metabolismo , Leucoencefalopatías/orina , Masculino , Ratones Endogámicos C57BL , Ratones Mutantes , Transportadores de Ácidos Monocarboxílicos/genética , Tomografía Computarizada de Emisión de Fotón Único , Sustancia Blanca/diagnóstico por imagenRESUMEN
Several subsets of dendritic cells (DCs) are present in the oropharyngeal tonsillar tissues and are thought to behave as major actors in development and regulation of immunity by acting as a first line of recognition for airborne and alimentary antigens. We previously discovered in human adult tonsils infected with Epstein-Barr virus (EBV), a subset of DCs that expressed langerin/CD207, a lectin usually recognized as a hallmark of epidermal Langerhans cells (LCs). In the present study, we analyzed the content of several child and adult tonsils in order to characterize in more detail the phenotype of these tonsillar CD207-expressing DCs (tCD207 DCs) and to compare it with that of other human DC subsets. We showed that all the human tonsils studied (n = 12) contained significant proportions of tCD207 DCs among tonsillar cells expressing HLA-DR. Moreover, the presence of tCD207 DCs in tonsils from young children free of EBV infection indicated that these cells could be established early in the tonsil independently of EBV infection. We also showed that tCD207 DCs, that were found mainly located within the tonsillar lymphoid stroma, were distinguishable from LCs by the level of expression of CD1a and EpCAM, and also from human inflammatory DCs by the lack of CD1a, CD206, and CD14 expression. Detailed analysis of cell surface DC markers showed that tCD207 DCs were unrelated to CD141(+) DCs or macrophages, but defined a subtype of tonsillar DCs closely related to myeloid resident CD1c DCs. Since it was established that blood CD1c myeloid DCs exhibit plasticity and are capable of expressing CD207 notably in the presence of inflammatory cytokines, it is tempting to speculate that CD207(+) CD1c(+) DCs may play a specific immune role.