Serum-free light chains as a dependable biomarker for stratifying patients with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND AND AIMS: Adaptive immunity is gaining a significant role in progression of metabolic dysfunction-associated steatotic liver disease (MASLD). B-cell activity can be assessed by serum-free light chains (sFLCs) k and λ levels. The objective of the present investigation is to examine the utility of sFLCs as non-invasive biomarkers for the stratification of MASLD. METHODS: We enrolled a consecutive cohort from an outpatient liver unit. Diagnosis of metabolic dysfunction-associated steatohepatitis (MASH) was made with liver biopsy according to current guidelines. Compensated advanced chronic liver disease (cACLD) and clinically significant portal hypertension (CSPH) were defined according to Baveno VII criteria. sFLCs were measured by turbidimetry using an immunoassay. RESULTS: We evaluated 254 patients, 162/254 (63.8%) were male. Median age was 54 years old, and the median body mass index was 28.4 kg/m2. A total of 157/254 (61.8%) subjects underwent liver biopsy: 88 had histological diagnosis of MASH, 89 were considered as simple metabolic dysfunction-associated steatotic liver (MASL) and 77/254 (30.3%) patients with compensated metabolic dysfunction-associated cirrhosis. By using Baveno VII criteria, 101/254 (39.7%) patients had cACLD; among them, 45/101 (44.5%) had CSPH. Patients with cACLD showed higher sFLC levels compared with patients without cACLD (p < .01), and patients with CSPH showed higher sFLC levels than patients without CSPH (p < .01). At multivariable analysis, sFLCs were associated with cACLD (p < .05) independently from γ-globulins and other known dysmetabolic risk factors. κFLC was associated with CSPH (p < .05) independently from γ-globulins and other known dysmetabolic risk factors. CONCLUSION: sFLCs could be a simple biomarker for stratification of cACLD in MASLD patients.

Mast cells and ocular surface: An update review.

Mast cells (MCs), traditionally viewed as key players in IgE-mediated allergic responses, are increasingly recognized for their versatile roles. Situated at critical barrier sites such as the ocular surface, these sentinel cells participate in a broad array of physiological and pathological processes. This review presents a comprehensive update on the immune pathophysiology of MCs, with a particular focus on the mechanisms underlying innate immunity. It highlights their roles at the ocular surface, emphasizing their participation in allergic reactions, maintenance of corneal homeostasis, neovascularization, wound healing, and immune responses in corneal grafts. The review also explores the potential of MCs as therapeutic targets, given their significant contributions to disease pathogenesis and their capacity to modulate immunity. Through a thorough examination of current literature, we aim to elucidate the immune pathophysiology and multifaceted roles of MCs in ocular surface health and disease, suggesting directions for future research and therapeutic innovation.

Trabectedin and Lurbinectedin Modulate the Interplay between Cells in the Tumour Microenvironment-Progresses in Their Use in Combined Cancer Therapy.

Trabectedin (TRB) and Lurbinectedin (LUR) are alkaloid compounds originally isolated from Ecteinascidia turbinata with proven antitumoral activity. Both molecules are structural analogues that differ on the tetrahydroisoquinoline moiety of the C subunit in TRB, which is replaced by a tetrahydro-ß-carboline in LUR. TRB is indicated for patients with relapsed ovarian cancer in combination with pegylated liposomal doxorubicin, as well as for advanced soft tissue sarcoma in adults in monotherapy. LUR was approved by the FDA in 2020 to treat metastatic small cell lung cancer. Herein, we systematically summarise the origin and structure of TRB and LUR, as well as the molecular mechanisms that they trigger to induce cell death in tumoral cells and supporting stroma cells of the tumoral microenvironment, and how these compounds regulate immune cell function and fate. Finally, the novel therapeutic venues that are currently under exploration, in combination with a plethora of different immunotherapeutic strategies or specific molecular-targeted inhibitors, are reviewed, with particular emphasis on the usage of immune checkpoint inhibitors, or other bioactive molecules that have shown synergistic effects in terms of tumour regression and ablation. These approaches intend to tackle the complexity of managing cancer patients in the context of precision medicine and the application of tailor-made strategies aiming at the reduction of undesired side effects.

Single cell transcriptomic analysis of Graves' disease thyroid glands reveals the broad immunoregulatory potential of thyroid follicular and stromal cells and implies a major re-interpretation of the role of aberrant HLA class II expression in autoimmunity.

The study of the immune response in thyroid autoimmunity has been mostly focused on the autoantibodies and lymphocytes, but there are indications that intrinsic features of thyroid tissue cells may play a role in disrupting tolerance that needs further investigation. The overexpression of HLA and adhesion molecules by thyroid follicular cells (TFC) and our recent demonstration that PD-L1 is also moderately expressed by TFCs in autoimmune thyroid indicates that TFCs they may activate but also inhibit the autoimmune response. Intriguingly, we have recently found that in vitro cultured TFCs are able to suppress the proliferation of autologous lymphocyte T in a contact-dependent manner which is independent of the PD-1/PD-L1 signaling pathway. To get a more comprehensive picture of TFC activating and inhibitory molecules/pathways driving the autoimmune response in the thyroid glands, preparations of TFCs and stromal cells from five Graves' disease (GD) and four control thyroid glands were compared by scRNA-seq. The results confirmed the previously described interferon type I and type II signatures in GD TFCs and showed unequivocally that they express the full array of genes that intervene in the processing and presentation of endogenous and exogeneous antigens. GD TFCs lack however expression of costimulatory molecules CD80 and CD86 required for priming T cells. A moderate overexpression of CD40 by TFCs was confirmed. GD Fibroblasts showed widespread upregulation of cytokine genes. The results from this first single transcriptomic profiling of TFC and thyroid stromal cells provides a more granular view of the events occurring in GD. The new data point at an important contribution of stromal cells and prompt a major re-interpretation of the role of MHC over-expression by TFC, from deleterious to protective. Most importantly this re-interpretation could also apply to other tissues, like pancreatic beta cells, where MHC over-expression has been detected in diabetic pancreas.

Distinct subsets of multi-lymphoid progenitors support ontogeny-related changes in human lymphopoiesis.

Changes in lymphocyte production patterns occurring across human ontogeny remain poorly defined. In this study, we demonstrate that human lymphopoiesis is supported by three waves of embryonic, fetal, and postnatal multi-lymphoid progenitors (MLPs) differing in CD7 and CD10 expression and their output of CD127-/+ early lymphoid progenitors (ELPs). In addition, our results reveal that, like the fetal-to-adult switch in erythropoiesis, transition to postnatal life coincides with a shift from multilineage to B lineage-biased lymphopoiesis and an increase in production of CD127+ ELPs, which persists until puberty. A further developmental transition is observed in elderly individuals whereby B cell differentiation bypasses the CD127+ compartment and branches directly from CD10+ MLPs. Functional analyses indicate that these changes are determined at the level of hematopoietic stem cells. These findings provide insights for understanding identity and function of human MLPs and the establishment and maintenance of adaptative immunity.

Thyroid cells from normal and autoimmune thyroid glands suppress T lymphocytes proliferation upon contact revealing a new regulatory inhibitory type of interaction independent of PD1/PDL1.

Immune Checkpoint Receptors include a number of inhibitory receptors that limit tissue damage during immune responses; blocking PD-1/PD-L1 checkpoint receptor axis led to a paradigm shift in cancer immunotherapy but also to autoimmune adverse effects, prominently thyroid autoimmunity. Although PD-L1 is known to be expressed on thyroid follicular cells (TFCs) of autoimmune glands the role on PD-1/PD-L1 in the interaction between T cells and thyroid cells in the tissue has not been investigated. Here we report that autologous primary TFCs, but not transformed TFCs, inhibit CD4 and CD8 T cell proliferation but no cytokine production. This effect is not, however, mediated by PD-1/PD-L1 nor locally produced cytokines. Beta galactosidase analysis excluded culture-induced senescence as an explanation. High resolution flow cytometry demonstrated that autologous TFC/T cells co-culture induced the expansion of several clusters of double negative (DN) T cells characterized by high expression of activation markers and negative immune checkpoints. Single cell transcriptomic profiling demonstrated that dissociated TFC express numerous candidate molecules for mediating this suppressive activity, including CD40, E-Cadherin and TIGIT ligands. These ligands directly or through the generation of a suppressor population of DN T cells, and not the PD-1/PD-L1 axis, are most likely the responsible of TFC immunosuppressive activity. These results contribute to reveal the complex network of inhibitory mechanism that operate at the tissue level to restrain autoimmunity but also point to pathways, other that PD-1/PD-L1, that can contribute to tumor evasion.

Receptor Mediated Effects of Advanced Glycation End Products (AGEs) on Innate and Adaptative Immunity: Relevance for Food Allergy.

As of late, evidence has been emerging that the Maillard reaction (MR, also referred to as glycation) affects the structure and function of food proteins. MR induces the conformational and chemical modification of food proteins, not only on the level of IgG/IgE recognition, but also by increasing the interaction and recognition of these modified proteins by antigen-presenting cells (APCs). This affects their biological properties, including digestibility, bioavailability, immunogenicity, and ultimately their allergenicity. APCs possess various receptors that recognize glycation structures, which include receptor for advanced glycation end products (RAGE), scavenger receptors (SRs), galectin-3 and CD36. Through these receptors, glycation structures may influence the recognition, uptake and antigen-processing of food allergens by dendritic cells (DCs) and monocytes. This may lead to enhanced cytokine production and maturation of DCs, and may also induce adaptive immune responses to the antigens/allergens as a result of antigen uptake, processing and presentation to T cells. Here, we aim to review the current literature on the immunogenicity of AGEs originating from food (exogenous or dietary AGEs) in relation to AGEs that are formed within the body (endogenous AGEs), their interactions with receptors present on immune cells, and their effects on the activation of the innate as well as the adaptive immune system. Finally, we review the clinical relevance of AGEs in food allergies.

Expression of CD49f defines subsets of human regulatory T cells with divergent transcriptional landscape and function that correlate with ulcerative colitis disease activity.

OBJECTIVE: Adoptive regulatory T cell (Treg) therapy is being trialled for the treatment of different autoimmune disorders, including inflammatory bowel diseases (IBD). In-depth understanding of the biological variability of Treg in the human blood may be required to improve IBD immune monitoring and treatment strategies. METHODS: Through a combination of quantitative proteomic, multiparametric flow cytometry, RNA-sequencing data analysis and functional assays on Treg enriched from the blood of ulcerative colitis (UC) patients and healthy controls, we investigated the association between CD49f expression, Treg phenotype and function, and UC disease activity. RESULTS: High-dimensional analysis and filtering defined two distinct subsets of human Treg based on the presence or absence of CD49f with divergent transcriptional landscape and functional activities. CD49f negative (CD49f-) Treg are enriched for functional Treg markers and present significantly increased suppressive capacity. In contrast, CD49fhigh Treg display a pro-inflammatory Th17-like phenotype and accumulate in the blood of patients with UC. Dysregulation on CD49f Treg subsets in patients with UC correlate with disease activity. CONCLUSION: Overall, our findings uncover the importance of CD49f expression on Treg in physiological immunity and in pathological autoimmunity.

[Immunity and tubular dysfunction in case of systemic disease]. / Immunité et dysfonctions tubulaires au cours des connectivites.

The immune renal tubular diseases are known since five decades, but their prevalence remains to be defined. They are caused by humoral and cellular effectors of innate and adaptative immunities on several targets of the renal tubule: protein channels, co or counter transporters, luminal or cytosolic enzymes, tight junctions. Genetic or epigenetic variations are also involved. Clinical manifestations are various and make the diagnosis difficult. They can precede the causal affection and they worsen the prognosis. The classical model consists in hypokalemic tubular distal acidosis observed in Sjögren's syndrome which illustrates the auto-immune epithelitis concept. Cellular immunity can act through other ways, like tertiary lymphoid neogenesis in systemic lupus. Humoral immunity through autoantibodies targets several membrane, cytosolic or nuclear proteins, causing specific tubular dysfonctions. It is also implied in the epithelial-mesenchymal transition of tubular cells. Innate immunity through cytokines may be involved. Treatment consists in electrolytic disorders correction and immunosupppressive medication: the choice should be guided at best by physiopathology.

New insights into oxidative stress and immune mechanisms involved in age-related macular degeneration tackled by novel therapies.

The prevalence of age-related macular degeneration (AMD) has increased in the last years. Although anti-VEGF agents have improved the prognosis of exudative AMD, dry AMD has still devastating effects on elderly people vision. Oxidative stress and inflammation are mechanisms involved in AMD pathogenesis and its progression. Molecular pathways involving epidermal growth factor receptor (EGFR), bone morphogenetic protein (BMP4) and the nuclear erythroid related factor 2 (Nrf2) are behind oxidative stress in AMD due to their participation in antioxidant cellular pathways. As a consequence of the disbalance produced in the antioxidant mechanisms, there is an activation of innate and adaptative immune response with cell recruitment, changes in complement factors expression, and modification of cellular milieu. Different therapies are being studied to treat dry AMD based on the possible effects on antioxidant molecular pathways or their action on the immune response. There is a wide range of treatments presented in this review, from natural antioxidant compounds to cell and gene therapy, based on their mechanisms. Finally, we hypothesize that alpha-1-antitrypsin (AAT), an anti-inflammatory and immunomodulatory molecule that can also modulate antioxidant cellular defenses, could be a good candidate for testing in AMD. This article is part of the special ssue on 'The Quest for Disease-Modifying Therapies for Neurodegenerative Disorders'.

Host immune responses in dermatophytes infection.

Dermatophytosis is a skin infection caused by keratinophilic, filamentous fungi. These are highly prevalent, common mycoses, affecting approximately 20% of the population. These fungi invade the stratum corneum, and other keratinised tissues, like nails and hair, where they grow by secreting enzymes and degrading keratin to obtain nutrients. Clinical presentation is variable and may depend on many factors, such as the infection site, the host's immunity and the dermatophyte's virulence. Generally, patients with acute superficial dermatophytosis mount cell-mediated immune responses. However, those suffering from chronic or recurrent infections are unable to develop this response, for reasons yet unknown. Several reports have described severe and occasionally life-threatening invasive diseases (deep dermatophytosis) associated with genetic mutations in the innate immunity-associated molecule CARD9, displaying the need to better understand its immune response. These dermatoses have substantial clinical consequences, producing chronic and difficult to treat skin lesions. They also lead to a decline in the patient's quality of life and impact their self-esteem. This review summarises findings on the immune response against dermatophytes.

The Micro-Immunotherapy Medicine 2LEID Exhibits an Immunostimulant Effect by Boosting Both Innate and Adaptive Immune Responses.

This study aimed at evaluating the effects of the micro-immunotherapy medicine (MIM) 2LEID, both in vitro and in vivo, on several components of the innate and adaptive immune system. MIM increased the phagocytic activity of macrophages, and it augmented the expression of the activation markers CD69 and HLA-DR in NK cells and monocytes/macrophages, respectively. The effect of MIM was evaluated in a model of respiratory infection induced by influenza A virus administration to immunocompetent mice in which it was able to improve neutrophil recruitment within the lungs (p = 0.1051) and slightly increased the circulating levels of IgM (p = 0.1655). Furthermore, MIM stimulated the proliferation of CD3-primed T lymphocytes and decreased the secretion of the immunosuppressive cytokine IL-10 in CD14+-derived macrophages. Human umbilical vein endothelial cells were finally used to explore the effect of MIM on endothelial cells, in which it slightly increased the expression of immune-related markers such as HLA-I, CD137L, GITRL, PD-L1 and ICAM-1. In conclusion, the present study suggests that MIM might be a promising nonspecific (without antigen specificity) immunostimulant drug in preventing and early treating respiratory infections, but not only exclusively, as it would gently support several facets of the immune system and host defenses.

Immunotherapeutic potential of Crotoxin: anti-inflammatory and immunosuppressive properties.

For the past 80 years, Crotoxin has become one of the most investigated isolated toxins from snake venoms, partially due to its major role as the main toxic component in the venom of the South American rattlesnake Crotalus durissus terrificus. However, in the past decades, progressive studies have led researchers to shift their focus on Crotoxin, opening novel perspectives and applications as a therapeutic approach. Although this toxin acts on a wide variety of biological events, the modulation of immune responses is considered as one of its most relevant behaviors. Therefore, the present review describes the scientific investigations on the capacity of Crotoxin to modulate anti-inflammatory and immunosuppressive responses, and its application as a medicinal immunopharmacological approach. In addition, this review will also discuss its mechanisms, involving cellular and molecular pathways, capable of improving pathological alterations related to immune-associated disorders.

Cellular and Molecular Immune Response to Chikungunya Virus Infection.

Chikungunya virus (CHIKV) is a re-emergent arthropod-borne virus (arbovirus) that causes a disease characterized primarily by fever, rash and severe persistent polyarthralgia. In the last decade, CHIKV has become a serious public health problem causing several outbreaks around the world. Despite the fact that CHIKV has been around since 1952, our knowledge about immunopathology, innate and adaptive immune response involved in this infectious disease is incomplete. In this review, we provide an updated summary of the current knowledge about immune response to CHIKV and about soluble immunological markers associated with the morbidity, prognosis and chronicity of this arbovirus disease. In addition, we discuss the progress in the research of new vaccines for preventing CHIKV infection and the use of monoclonal antibodies as a promising therapeutic strategy.

Immunotherapeutic potential of Crotoxin: anti-inflammatory and immunosuppressive properties

For the past 80 years, Crotoxin has become one of the most investigated isolated toxins from snake venoms, partially due to its major role as the main toxic component in the venom of the South American rattlesnake Crotalus durissus terrificus. However, in the past decades, progressive studies have led researchers to shift their focus on Crotoxin, opening novel perspectives and applications as a therapeutic approach. Although this toxin acts on a wide variety of biological events, the modulation of immune responses is considered as one of its most relevant behaviors. Therefore, the present review describes the scientific investigations on the capacity of Crotoxin to modulate anti-inflammatory and immunosuppressive responses, and its application as a medicinal immunopharmacological approach. In addition, this review will also discuss its mechanisms, involving cellular and molecular pathways, capable of improving pathological alterations related to immune-associated disorders.(AU)

Receptores tipo Toll, patogénesis y respuesta inmune a Helicobacter pylori / Toll-like receptors, pathogenesis and immune response to Helicobacter pylori

Helicobacter pylori coloniza el epitelio gástrico y la mayoría de las personas infectadas es asintomática, de 10 al 20 por ciento desarrolla gastritis atrófica, úlcera péptica, y menos de 3 por ciento genera cáncer gástrico. Estas patologías están determinadas por la relación entre los factores de virulencia de la bacteria y los factores del hospedero como predisposición genética y respuesta inmune. La inmunidad innata, representada principalmente por los receptores tipo Toll y tipo Nod, reconocen a sus ligandos específicos y activan factores de transcripción como NF-kB, AP-1, CREB-1, induciendo la producción de citocinas inflamatorias como IL-8, IL-12, IL-6, IL-1β, IL-18 y TNF-α, e IL-10. La inflamación crónica favorece los cambios de morfología gástrica, evita la apoptosis y favorece la angiogénesis, ocasionando lesiones neoplásicas y cáncer. El objetivo de esta revisión es analizar los mecanismos propuestos a la fecha de la respuesta inmune innata y adaptativa, involucrados en la infección por H. pylori, y se puntualiza en los mecanismos de eliminación o persistencia de la infección.

Helicobacter pylori colonize the gastric epithelial, most infected people are asymptomatic, 10 to 20 percent develop atrophic gastritis, peptic ulcer and less than 3 percent gastric cancer. These diseases are determined by the relationship between virulence factors of bacteria, host factors such as, genetic predisposition, and immune response. The innate immune response mainly represented by Toll-like receptors and Nod-like receptors that recognize their specific ligands, activate transcription factors as NF-kB, AP-1, CREB-1, inducing production of inflammatory cytokines such as IL -8, IL-12, IL-6, IL-1β, IL-18, TNF-α and IL-10. Chronic inflammation promotes gastric morphological changes, prevents apoptosis and allows angiogenesis generating neoplasic lesions and cancer. The aim of this review is to analyze the mechanisms proposed to date of the innate and adaptative immune response involved in H. pylori infection; remarking the mechanisms related in the elimination or persistence.

La vitamina D, el sistema inmune y las enfermedades de la piel / Vitamin D, immune system and skin diseases

El sistema endocrino de la vitamina D tiene un rol esencial en la regulación del metabolismo óseo y la homeostasis del calcio. Sin embargo, los hallazgos de las últimas décadas han revelado un amplio rango de acciones que incluyen la regulación de la diferenciación y proliferación celular y la modulación del sistema inmune y otros sistemas endocrinos. A través de la regulación de la inmunidad innata y adquirida participa en la regulación de la respuesta a diversos antígenos. Estas nuevas acciones sugieren que la vitamina D es un factor ambiental con un rol importante en el desarrollo de enfermedades autoinmunes. El nuevo rol modulador de la vitamina D en el sistema inmune ha dado explicación a muchos fenómenos antes desconocidos y ha abierto nuevas oportunidades en el tratamiento de las enfermedades inflamatorias.

The vitamin D endocrine system plays an essential role in calcium ho-meostasis and bone metabolism. Nevertheless, research during the pastdecades has revealed a diverse range of biological actions that includeinduction of cell diff erentiation, inhibition of cell growth,immunomodulation, and control of other hormonal systems.Through the innate and adaptative immune systems modulation, vitamin D regulates the response to many antigens. These new actions suggest an importantrole for vitamin D as a modifi able environmental factor in autoimmune disease.The new fi ndings on vitamin D actions on immunity have explained its role in the pathogenesis of skin autoimmune diseases, and have offered new possibilities for their treatment.

Respuesta inmunitaria de la enfermedad de Hansen: revisión / Immune response of Hansen´s disease: review

La enfermedad de Hansen presenta un amplio espectro de manifestaciones clínicas e histopatológicas, las cuales son un reflejo de la naturaleza de la respuesta inmunológica del individuo ante diversos componentes del Mycobacterium leprae. El sistema inmunológico, integrado por la existencia de una inmunidad innata y adaptativa, ofrece protección frente a infecciones de diversas etiologías, entre ellas las bacterianas. Por supuesto las bacterias han logrado desarrollar múltiples estrategias para evadir las defensas del hospedador, que se basan en mecanismos algunos muy complejos y otros más simples, pero con una sola finalidad de “resistir” el ataque del hospedador y lograr sobrevivir. Estudios realizados en la enfermedad de Hansen han podido determinar los diferentes componentes que puedan estar actuando tanto en la inmunidad innata cómo en la adquirida. En este trabajo se trata de resumir algunos estudios recientes en la enfermedad de Hansen con mayor énfasis en el área de inmunología, sin dejar de considerar que toda enfermedad debe estar muy ligada a otros aspectos tan igual de importantes cómo son los sociales, ambientales y otros de muy difícil resolución en un laboratorio.

Hansen’s disease presents a wide spectrum of clinical and histopathological manifestations that reflect the nature of the immunological response of the host towards diverse Mycobacterium leprae components. The immunological system, composed by both innate and adaptive immunology, offers protection towards infections of various etiologies, among them bacterial. Bacteria, of course, have developed multiple strategies for evading host defenses, based on either very complex or simple mechanisms, but with a single purpose: to “resist” host attacks and to be able to survive. We have tried to summarize some recent studies in Hansen’s disease, with more emphasis in the inmunology area. We think that in the future, all illnesses should also be very strongly related to other important aspects such as the social, environmental and economic, and whose development is not solved in a laboratory.

Fundamental mechanisms of immune response to oral bacteria and the main perspectives of a vaccine against dental caries: a brief review / Mecanismos fundamentais de resposta imune contra bactérias bucais e as principais perspectivas para uma vacina anticárie: uma breve revisão

Dental caries may be defined as a complex multifatorial disease in that a broad group of biological, socio-economic and cultural factors interact directly or indirectly in the establishment and colonization of cariogenic microorganisms within the microbial community of the dental biofilm. Innate and adaptative immunity are two fundamental aspects of the immune system response against infections, such as dental caries. Besides, the majority of pathogenic infectious agents enter the organisms by the oral route. Consequently, the mucosal tissue, associated exocrine glands and saliva contributes to the protection of the oral cavity because contain cells responsible for antigen internalization and antibodies specific to oral bacteria. Macrophages are phagocytic cells that can internalize and kill bacteria by several mechanisms of internalization, including endocytosis, macropinocytosis and phagocytosis. Streptococcus mutans is the major pathogen of dental caries due to its ability to adhere and accumulate on tooth surfaces, using different virulence factors (AgI/II, Gtf, Gbps). Recent studies demonstrated protection against experimentally induced dental caries for vaccines containing intact or peptides from antigen I/II, Gtf or Gbp and vaccines containing a combination of antigens. The present review summarizes the fundamental mechanisms of host immune responses to oral bacteria and the main perspectives of a vaccine against dental caries.

A cárie dentária pode ser definida como uma doença complexa multifatorial causada por fatores biológicos, socioeconômicos e culturais que interagem direta ou indiretamente na colonização e estabelecimento de microrganismos cariogênicos na comunidade microbiana do biofilme dentário. As imunidades inata e adaptativa são os dois aspectos fundamentais de resposta do sistema imune contra infecções, como a cárie dentária. Além disso, a maioria dos agentes infecciosos patogênicos entra no organismo por via oral. Consequentemente, o tecido mucoso, associado com as glândulas exócrinas e a saliva contribuem para a proteção da cavidade bucal por conterem células responsáveis pela internalização de antígenos ou anticorpos contra as bactérias bucais. Os macrófagos são células fagocíticas que podem internalizar e eliminar bactérias por diversos mecanismos de internalização, como a endocitose, macropinocitose e fagocitose. Streptococcus mutans é o principal patógeno da cárie dentária por sua habilidade em aderir e acumular nas superfícies dentárias, usando diferentes fatores de virulência (AgI/II, Gtf e Gbps). Estudos recentes têm demonstrado proteção contra cárie induzida experimentalmente utilizando vacinas contendo antígenos intactos ou peptídeos a partir de AgI/II, Gtf ou Gbps ou uma combinação de antígenos. A presente revisão sumariza os mecanismos fundamentais de resposta imune contra bactérias bucais e as principais perspectivas de uma vacina anticárie.