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1.
Science ; 371(6526)2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33446526

RESUMO

Human monogenic disorders have revealed the critical contribution of type 17 responses in mucosal fungal surveillance. We unexpectedly found that in certain settings, enhanced type 1 immunity rather than defective type 17 responses can promote mucosal fungal infection susceptibility. Notably, in mice and humans with AIRE deficiency, an autoimmune disease characterized by selective susceptibility to mucosal but not systemic fungal infection, mucosal type 17 responses are intact while type 1 responses are exacerbated. These responses promote aberrant interferon-γ (IFN-γ)- and signal transducer and activator of transcription 1 (STAT1)-dependent epithelial barrier defects as well as mucosal fungal infection susceptibility. Concordantly, genetic and pharmacologic inhibition of IFN-γ or Janus kinase (JAK)-STAT signaling ameliorates mucosal fungal disease. Thus, we identify aberrant T cell-dependent, type 1 mucosal inflammation as a critical tissue-specific pathogenic mechanism that promotes mucosal fungal infection susceptibility in mice and humans.


Assuntos
Candida albicans/imunologia , Candidíase Mucocutânea Crônica/genética , Candidíase Mucocutânea Crônica/imunologia , Imunidade nas Mucosas/imunologia , Poliendocrinopatias Autoimunes/genética , Poliendocrinopatias Autoimunes/imunologia , Adolescente , Adulto , Idoso , Animais , Modelos Animais de Doenças , Feminino , Humanos , Imunidade nas Mucosas/genética , Vigilância Imunológica/genética , Vigilância Imunológica/imunologia , Interferon gama/genética , Interleucinas/genética , Janus Quinases/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Mucosa Bucal/imunologia , Mucosa Bucal/patologia , Receptores de Interleucina-17/genética , Fator de Transcrição STAT1/genética , Linfócitos T/imunologia , Adulto Jovem
3.
Scand J Immunol ; 92(5): e12973, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32889730

RESUMO

Behçet's disease (BD) is a heterogeneous multi-organ disorder in search of a unified pathophysiological theory and classification. The disease frequently has overlapping features resembling other disease clusters, such as vasculitides, spondyloarthritides and thrombophilias with similar genetic risk variants, namely HLA-B*51, ERAP1, IL-10, IL-23R. Many of the BD manifestations, such as unprovoked recurrent episodes of inflammation and increased expression of IL-1, IL-6 and TNFα, overlap with those of the hereditary monogenic autoinflammatory syndromes, positioning BD at the crossroads between autoimmune and autoinflammatory syndromes. BD-like disease associates with various inborn errors of immunity, including familial Mediterranean fever, conditions related to dysregulated NF-κB activation (eg TNFAIP3, NFKB1, OTULIN, RELA, IKBKG) and either constitutional trisomy 8 or acquired trisomy 8 in myelodysplastic syndromes. We review here the recent advances in the immunopathology of BD, BD-like diseases and the NF-κB pathway suggesting new elements in the elusive BD etiopathogenesis.


Assuntos
Síndrome de Behçet/imunologia , Cromossomos Humanos Par 8/imunologia , NF-kappa B/imunologia , Trissomia/imunologia , Síndrome de Behçet/genética , Síndrome de Behçet/patologia , Cromossomos Humanos Par 8/genética , Predisposição Genética para Doença/genética , Humanos , Interleucina-10/genética , Interleucina-10/imunologia , Mucosa Bucal/imunologia , Mucosa Bucal/metabolismo , Mucosa Bucal/patologia , NF-kappa B/genética , NF-kappa B/metabolismo , Fenótipo , Úlcera Cutânea/genética , Úlcera Cutânea/imunologia , Úlcera Cutânea/patologia , Trissomia/genética
4.
PLoS One ; 15(9): e0238425, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32960889

RESUMO

OBJECTIVE: To evaluate the effects of Bifidobacterium animalis subsp. lactis HN019 (HN019) on clinical periodontal parameters (plaque accumulation and gingival bleeding), on immunocompetence of gingival tissues [expression of beta-defensin (BD)-3, toll-like receptor 4 (TLR4), cluster of differentiation(CD)-57 and CD-4], and on immunological properties of saliva (IgA levels) in non-surgical periodontal therapy in generalized chronic periodontitis (GCP) patients. Adhesion to buccal epithelial cells (BEC) and the antimicrobial properties of HN019 were also investigated. MATERIALS AND METHODS: Thirty patients were recruited and monitored clinically at baseline (before scaling and root planing-SRP) and after 30 and 90 days. Patients were randomly assigned to Test (SRP+Probiotic, n = 15) or Control (SRP+Placebo, n = 15) group. Probiotic lozenges were used for 30 days. Gingival tissues and saliva were immunologically analyzed. The adhesion of HN019 with or without Porphyromonas gingivalis in BEC and its antimicrobial properties were investigated in in vitro assays. Data were statistically analyzed (p<0.05). RESULTS: Test group presented lower plaque index (30 days) and lower marginal gingival bleeding (90 days) when compared with Control group. Higher BD-3, TLR4 and CD-4 expressions were observed in gingival tissues in Test group than in Control group. HN019 reduced the adhesion of P. gingivalis to BEC and showed antimicrobial potential against periodontopathogens. CONCLUSION: Immunological and antimicrobial properties of B. lactis HN019 make it a potential probiotic to be used in non-surgical periodontal therapy of patients with GCP. CLINICAL RELEVANCE: B. lactis HN019 may be a potential probiotic to improve the effects of non-surgical periodontal therapy. Name of the registry and registration number (ClinicalTrials.gov): "Effects of probiotic therapy in the treatment of periodontitis"-NCT03408548.


Assuntos
Bifidobacterium animalis/imunologia , Periodontite Crônica/terapia , Probióticos/uso terapêutico , Adulto , Aderência Bacteriana/imunologia , Infecções por Bacteroidaceae/imunologia , Infecções por Bacteroidaceae/microbiologia , Infecções por Bacteroidaceae/terapia , Periodontite Crônica/imunologia , Periodontite Crônica/microbiologia , Método Duplo-Cego , Feminino , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Imunoglobulina A Secretora/metabolismo , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/imunologia , Mucosa Bucal/microbiologia , Porphyromonas gingivalis/patogenicidade , Saliva/imunologia
5.
Oral Dis ; 26 Suppl 1: 69-79, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32862519

RESUMO

A crucial aspect of mucosal HIV transmission is the interaction between HIV, the local environmental milieu and immune cells. The oral mucosa comprises many host cell types including epithelial cells, CD4 + T cells, dendritic cells and monocytes/macrophages, as well as a diverse microbiome predominantly comprising bacterial species. While the oral epithelium is one of the first sites exposed to HIV through oral-genital contact and nursing infants, it is largely thought to be resistant to HIV transmission via mechanisms that are still unclear. HIV-1 infection is also associated with predisposition to secondary infections, such as tuberculosis, and other diseases including cancer. This review addresses the following questions that were discussed at the 8th World Workshop on Oral Health and Disease in AIDS held in Bali, Indonesia, 13 September -15 September 2019: (a) How does HIV infection affect epithelial cell signalling? (b) How does HIV infection affect the production of cytokines and other innate antimicrobial factors, (c) How is the mucosal distribution and function of immune cells altered in HIV infection? (d) How do T cells affect HIV (oral) pathogenesis and cancer? (e) How does HIV infection lead to susceptibility to TB infections?


Assuntos
Infecções por HIV , Imunidade Inata , Mucosa Bucal , Linfócitos T CD4-Positivos , Infecções por HIV/imunologia , Humanos , Imunidade nas Mucosas , Lactente , Mucosa Bucal/imunologia , Mucosa Bucal/virologia
6.
PLoS One ; 15(8): e0236141, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764751

RESUMO

BACKGROUND: Novel interventions are needed to reach young people and adult men with HIV services given the low HIV testing rates in these population sub-groups. We assessed the feasibility and acceptability of a peer-led oral HIV self-testing (HIVST) intervention in Kasensero, a hyperendemic fishing community (HIV prevalence: 37-41%) in Rakai, Uganda. METHODS: This study was conducted among young people (15-24 years) and adult men (25+ years) between May and August 2019. The study entailed distribution of HIVST kits by trained "peer-leaders," who were selected from existing social networks and trained in HIVST distribution processes. Peer-leaders received up to 10 kits to distribute to eligible social network members (i.e. aged 15-24 years if young people or 25+ years if adult man, not tested in the past 3 months, and HIV-negative or of unknown HIV status at enrolment). The intervention was evaluated against the feasibility benchmark of 70% of peer-leaders distributing up to 70% of the kits that they received; and the acceptability benchmark of >80% of the respondents self-testing for HIV. RESULTS: Of 298 enrolled into the study at baseline, 56.4% (n = 168) were young people (15-24 years) and 43.6% (n = 130) were adult males (25+ years). Peer-leaders received 298 kits and distributed 296 (99.3%) kits to their social network members. Of the 282 interviewed at follow-up, 98.2% (n = 277) reported that they used the HIVST kits. HIV prevalence was 7.4% (n = 21). Of the 57.1% (n = 12) first-time HIV-positives, 100% sought confirmatory HIV testing and nine of the ten (90%) respondents who were confirmed as HIV-positive were linked to HIV care within 1 week of HIV diagnosis. CONCLUSION: Our findings show that a social network-based, peer-led HIVST intervention in a hyperendemic fishing community is highly feasible and acceptable, and achieves high linkage to HIV care among newly diagnosed HIV-positive individuals.


Assuntos
Autoavaliação Diagnóstica , Infecções por HIV/diagnóstico , Programas de Rastreamento/psicologia , Infuência dos Pares , Autocuidado/psicologia , Adolescente , Adulto , Doenças Endêmicas , Estudos de Viabilidade , Seguimentos , Anticorpos Anti-HIV/isolamento & purificação , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Liderança , Masculino , Masculinidade , Programas de Rastreamento/instrumentação , Programas de Rastreamento/métodos , Mucosa Bucal/imunologia , Projetos Piloto , Prevalência , Kit de Reagentes para Diagnóstico , População Rural/estatística & dados numéricos , Autocuidado/instrumentação , Autocuidado/métodos , Uganda/epidemiologia , Adulto Jovem
7.
J Cancer Res Ther ; 16(3): 445-451, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719249

RESUMO

Introduction: Several studies regarding tumor-stroma ratio (TSR) in colorectal, esophageal, breast, endometrial, and cervical carcinomas have been done in the past with significant results. Objectives: The objectives of this study were to (1) study and grade TSR in buccal mucosa and tongue squamous cell carcinoma (SCC), (2) grade inflammatory cell infiltrate surrounding the tumor, and (3) correlate the above two parameters with tumor grade, lymph node metastasis, lymphovascular invasion (LVI), and perineural invasion (PNI). Materials and Methods: Totally, 25 patients of buccal SCC and 16 cases of tongue SCC were included in the study. TSR was assessed visually on the hematoxylin and eosin-stained tissue sections by two independent observers. Cases were categorized into two groups: One with high TSR >50% (stroma poor) and the other with low TSR <50% as the stroma-rich group. TSR was correlated with tumor size, lymph node metastasis, inflammatory cell infiltrate, LVI, and PNI. Data were analyzed by the Statistical Package for the Social Sciences version 16.0 (Chicago, IL, USA) for Windows. The Chi-square and Fischer's exact tests were applied in the analysis of categorical variable. Results and Conclusion: SCC of buccal mucosa showed a significant correlation between TSR and size of the tumor (P = 0.001). We found that smaller the tumor size ≤2 cm (Stage T1), lesser the TSR, and size >2 cm was found to be associated with higher TSR. Hence, higher TSR (stroma poor) was associated with an adverse pathological characteristic, i.e., advanced T significantly. There was no significant correlation between TSR and inflammatory infiltrate with grade of the tumor, lymph node metastasis, LVI, and PNI. In 16 cases of SCC of the tongue; no correlation was observed between TSR and inflammatory infiltrate with tumor size, grade of the tumor, lymph node metastasis, LVI, and PNI. TSR has been studied in various malignancies (mostly adenocarcinomas) including laryngeal SCCs; however, it has never been studied on oral SCCs.


Assuntos
Carcinoma de Células Escamosas/patologia , Mucosa Bucal/patologia , Neoplasias Bucais/patologia , Células Estromais/patologia , Neoplasias da Língua/patologia , Língua/patologia , Adulto , Idoso , Carcinoma de Células Escamosas/imunologia , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/imunologia , Neoplasias Bucais/imunologia , Gradação de Tumores , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de Risco , Células Estromais/imunologia , Língua/imunologia , Neoplasias da Língua/imunologia , Adulto Jovem
8.
Adv Exp Med Biol ; 1195: 151-154, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32468470

RESUMO

Drug addiction is a chronic relapsing disorder and a burden to society and individuals. The toxicity induced by drugs related with addiction may trigger dysfunction and death of cells of the central nervous system. The study of alterations of proteins and biomarkers in buccal cells would be beneficial in understanding drug addiction, as the buccal mucosa is of ectodermal origin such as the central nervous system. METHOD: Buccal smears of 35 individuals with addictive disorders (20) or substance use disorders (15) for more than 3 years were collected by the gentle brushing of the inside of the cheeks. Immunocytochemical staining of IL-1ß, IL-6, TNF-α, NFKß, bcl-2, and ucp4 was performed on the epithelial cells, for the study of oxidative stress, toxicity, and inflammation. Papanicolaou staining was also performed for the potential structural disorders. There was a correlation with the clinical profile of each individual. None of the individuals was HIV or Tbc positive. RESULTS: Cytomorphology and immunoprofile of the smears of chronic relapsers and substance users for more than 3 years revealed karyolitic cells undergoing necrosis and increased expression of the markers IL-1ß, IL-6, TNF-α, and NFKß. Decreased expression of bcl2 was correlated with increased expression of ucp4. CONCLUSION: The literature in the area of addiction is growing rapidly; however, the results are still mixed. Given the complexity of the problem, the goal should be the discovery of a minimal invasive and inexpensive diagnostic procedure to identify a prognostic and therapeutic target. The correlation of the expression of biomarkers on buccal cells could be valuable for the design of predictive and therapeutic strategies.


Assuntos
Biomarcadores/análise , Mucosa Bucal/metabolismo , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Transtornos Relacionados ao Uso de Substâncias/terapia , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/patologia , Mucosa Bucal/imunologia , Mucosa Bucal/patologia , Estresse Oxidativo , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/metabolismo
9.
PLoS One ; 15(3): e0229065, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32126095

RESUMO

Porcine Reproductive and Respiratory Syndrome (PRRS) is a complex model of host/virus relationship. Disease control measures often includes "acclimatization", i.e. the exposure of PRRS-naïve gilts and sows to PRRSV-infected pigs and premises before the breeding period. In this respect, we had repeatedly observed an association between PRRSV-specific IgA responses in oral fluids (OF) of gilts and block of PRRSV spread. Therefore, we set out to investigate in vitro the inhibition of PRRSV replication by OF samples with different titers of PRRSV-specific IgA and IgG antibody, using Real-time RT PCR. PRRSV yield reduction in monocyte-derived macrophages was associated with the IgA content in OF samples, whereas the IgG-rich samples were sometimes associated with antibody-dependent enhancement (ADE) of replication. Accordingly, we could discriminate between ADE-positive and ADE-negative PRRSV strains. Next, we separated Ig isotypes in OF samples of PRRSV-infected pigs by means of protein A and size exclusion chromatography. The above results were confirmed by using separated Ig isotypes. Both dimeric and monomeric IgA were associated with the strongest reduction of PRRSV replication. The treatment of pig macrophages with separated OF antibodies before PRRSV infection was also associated with PRRSV yield reduction, along with clear changes of both CD163 and CD169 surface expression. Our results point at a role of mucosal IgA in the control of PRRSV replication by extra- and/or intracellular interaction with PRRSV, as well as by induction of signals leading to a reduced susceptibility of macrophages to PRRSV infection.


Assuntos
Líquidos Corporais/imunologia , Imunoglobulina A/análise , Boca/imunologia , Síndrome Respiratória e Reprodutiva Suína/imunologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/imunologia , Animais , Anticorpos Antivirais/análise , Anticorpos Antivirais/metabolismo , Líquidos Corporais/virologia , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Feminino , Imunidade nas Mucosas/fisiologia , Imunoglobulina A/metabolismo , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/patologia , Boca/virologia , Mucosa Bucal/imunologia , Mucosa Bucal/patologia , Síndrome Respiratória e Reprodutiva Suína/metabolismo , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , Reação em Cadeia da Polimerase em Tempo Real , Suínos , Proteínas Virais/genética
10.
Indian J Dermatol Venereol Leprol ; 86(3): 233-239, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31898637

RESUMO

Background: Pemphigus vulgaris is a potentially fatal autoimmune epidermal blistering disease with a chronic and relapsing course. It is difficult to predict clinical relapse. Identification of clinical and immunological factors that are associated with early clinical relapse in a prospective study design may help in planning treatment for better maintenance of clinical remission. Aim: The aim of our study was to identify clinical and immunological factors associated with clinical relapse within 9 months of study inclusion in patients with pemphigus vulgaris in clinical remission. Methods: Forty consecutive consenting patients who had been diagnosed to have pemphigus vulgaris and were in clinical remission on minimal therapy or off therapy were included. The patients were followed up every 3 months until 9 months. Clinical factors considered relevant were recorded at the beginning of the study. Immunological factors such as CD19+ B-cell count and CD19+CD27+ memory B cells/plasma cell count in peripheral blood were assessed at baseline [anti-desmoglein (Dsg) 1 and 3 titers were first assessed at 3 months, not at baseline] and repeated every 3 months, until 9 months or clinical relapse whichever was earlier. Direct immunofluorescence (DIF) of skin biopsy specimen was performed at study initiation and again at the time of clinical relapse or study completion, whichever occurred earlier. All patients completed the study. Results: Of 40 patients, 11 (27.5%) experienced relapse as per definition, while 29 (72.5%) remained in complete remission. Clinical relapse during study duration was significantly more common in those who had onset of disease in oral mucosa [odds ratio (OR), 10.71; 95% confidence interval (CI) 1.21-94.86, P = 0.02], pruritus (OR 8.4; 95% CI 1.76-40.02, P = 0.01), and extensive cutaneous involvement during previous disease activity (OR 7.36; 95% CI 1.34-40.55, P = 0.03) and also pruritus during remission (P = 0.004). Immunological factors found to be significantly associated with early clinical relapse were raised CD19+ B-cell count at baseline (OR 7.84; 95% CI 1.39 - 53.41, P = 0.01), immunoglobulin G (OR 4.85; 95% CI 1.09-23.44, P = 0.04), and C3 (OR 20.33; 95% CI 3.02-199.5, P < 0.001) positivity in the intercellular space of the epidermis on DIF at study onset and rising anti-Dsg 3 antibody titers (OR 19.96; 95% CI 1.85- 310.9, P = 0.03). Limitations: Limited sample size, short follow-up duration, and inability to perform anti-Dsg enzyme linked immunosorbent assay for all the patients at all the time points of assessment are limitations of this study. Conclusion: Immunological relapse can be determined before clinical relapse, so that treatment can be restarted/modified and clinical remission can be maintained.


Assuntos
Fatores Imunológicos/imunologia , Pênfigo/diagnóstico , Pênfigo/imunologia , Adulto , Idoso , Autoanticorpos/sangue , Autoanticorpos/imunologia , Feminino , Seguimentos , Humanos , Fatores Imunológicos/sangue , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/imunologia , Mucosa Bucal/patologia , Pênfigo/sangue , Estudos Prospectivos , Recidiva , Indução de Remissão
11.
Sci Immunol ; 5(43)2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31901072

RESUMO

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.


Assuntos
Interações Hospedeiro-Patógeno/imunologia , Interleucina-17/imunologia , Mucosa Bucal/imunologia , Mucosa Bucal/microbiologia , Células Th17/imunologia , Animais , Humanos , Imunidade nas Mucosas , Microbiota , Doenças da Boca/imunologia , Doenças da Boca/microbiologia
12.
Gut Microbes ; 11(2): 237-244, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31347944

RESUMO

Although exclusive breastfeeding has been linked to lower rates of postnatal HIV transmission compared to nonexclusive breastfeeding, mechanisms underlying this are unclear. Across a longitudinally sampled cohort of South African infants, we showed that exclusively breastfed (EBF) infants had altered gut bacterial communities when compared to nonexclusively breastfed (NEBF) infants, as well as reduced peripheral CD4 + T cell activation and lowered chemokine and chemokine receptor expression in the oral mucosa. We further demonstrated that the relative abundance of key taxa was correlated with peripheral CD4 + T cell activation. Here, we supplement those findings by using compositional data analyses to identify shifts in the abundance of several Bifidobacteria strains relative to select strains of Escherichia, Bacteroides, and others that are associated with the transition to NEBF. We illustrate that the abundance ratio of these taxa is tightly correlated with feeding modality and is a strong predictor of peripheral T cell activation. More broadly, we discuss our study in the context of novel developments and explore future directions for the field.


Assuntos
Bactérias/classificação , Aleitamento Materno , Microbioma Gastrointestinal , Linfócitos Intraepiteliais/metabolismo , Bactérias/genética , Bactérias/isolamento & purificação , Bacteroides/genética , Bacteroides/isolamento & purificação , Bifidobacterium/genética , Bifidobacterium/isolamento & purificação , Contagem de Linfócito CD4 , Estudos de Coortes , Escherichia/genética , Escherichia/isolamento & purificação , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/imunologia , Genes Bacterianos , Infecções por HIV/imunologia , Infecções por HIV/transmissão , Humanos , Lactente , Recém-Nascido , Transmissão Vertical de Doença Infecciosa , Estudos Longitudinais , Metagenômica , Mucosa Bucal/imunologia , Mucosa Bucal/metabolismo , Mucosa Bucal/microbiologia , Análise de Componente Principal , RNA Ribossômico 16S/genética , Receptores de Quimiocinas/metabolismo , África do Sul/epidemiologia , Subpopulações de Linfócitos T/metabolismo
14.
Sci Transl Med ; 11(521)2019 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-31801887

RESUMO

CCR5 is thought to play a central role in orchestrating migration of cells in response to inflammation. CCR5 antagonists can reduce inflammatory disease processes, which has led to an increased interest in using CCR5 antagonists in a wide range of inflammation-driven diseases. Paradoxically, these antagonists appear to function without negatively affecting host immunity at barrier sites. We reasoned that the resolution to this paradox may lie in the CCR5+ T cell populations that permanently reside in tissues. We used a single-cell analysis approach to examine the human CCR5+ T cell compartment in the blood, healthy, and inflamed mucosal tissues to resolve these seemingly contradictory observations. We found that 65% of the CD4 tissue-resident memory T (TRM) cell compartment expressed CCR5. These CCR5+ TRM cells were enriched in and near the epithelial layer and not only limited to TH1-type cells but also contained a large TH17-producing and a stable regulatory T cell population. The CCR5+ TRM compartment was stably maintained even in inflamed tissues including the preservation of TH17 and regulatory T cell populations. Further, using tissues from the CHARM-03 clinical trial, we found that CCR5+ TRM are preserved in human mucosal tissue during treatment with the CCR5 antagonist Maraviroc. Our data suggest that the human CCR5+ TRM compartment is functionally and spatially equipped to maintain barrier immunity even in the absence of CCR5-mediated, de novo T cell recruitment from the periphery.


Assuntos
Compartimento Celular , Inflamação/imunologia , Receptores CCR5/metabolismo , Linfócitos T/citologia , Linfócitos T/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/metabolismo , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Compartimento Celular/efeitos dos fármacos , Citocinas/biossíntese , Feminino , Humanos , Lectinas Tipo C/metabolismo , Subpopulações de Linfócitos/efeitos dos fármacos , Subpopulações de Linfócitos/imunologia , Masculino , Maraviroc/farmacologia , Pessoa de Meia-Idade , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/imunologia , Mucosa Bucal/patologia , Receptores de Antígenos de Linfócitos T/metabolismo , Linfócitos T/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Transcriptoma/genética , Adulto Jovem
15.
Adv Gerontol ; 32(4): 602-605, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31800190

RESUMO

This article presents the results of a study of the dental status of 60 elderly and senile patients with squamous cell carcinoma of the oral mucosa. The use of removable and non-removable dentures, carious lesions of teeth, dental plaque, sharp edges of the crown seals were studied as components of the dental status.


Assuntos
Carcinoma de Células Escamosas , Mucosa Bucal , Neoplasias Bucais , Saúde Bucal , Idoso , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Cárie Dentária/complicações , Humanos , Mucosa Bucal/imunologia , Mucosa Bucal/patologia , Neoplasias Bucais/complicações , Neoplasias Bucais/imunologia , Neoplasias Bucais/patologia , Saúde Bucal/estatística & dados numéricos
16.
Sci Rep ; 9(1): 15779, 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31673005

RESUMO

The gingival epithelium is a physical and immunological barrier to the microbiota of the oral cavity, which interact through soluble mediators with the immune cells that patrol the tissue at the gingival epithelium. We sought to develop a three-dimensional gingivae-biofilm interface model using a commercially available gingival epithelium to study the tissue inflammatory response to oral biofilms associated with "health", "gingivitis" and "periodontitis". These biofilms were developed by sequential addition of microorganisms to mimic the formation of supra- and sub-gingival plaque in vivo. Secondly, to mimic the interactions between gingival epithelium and immune cells in vivo, we integrated peripheral blood mononuclear cells and CD14+ monocytes into our three-dimensional model and were able to assess the inflammatory response in the immune cells cultured with and without gingival epithelium. We describe a differential inflammatory response in immune cells cultured with epithelial tissue, and more so following incubation with epithelium stimulated by "gingivitis-associated" biofilm. These results suggest that gingival epithelium-derived soluble mediators may control the inflammatory status of immune cells in vitro, and therefore targeting of the epithelial response may offer novel therapies. This multi-cellular interface model, both of microbial and host origin, offers a robust in vitro platform to investigate host-pathogens at the epithelial surface.


Assuntos
Bactérias/imunologia , Fenômenos Fisiológicos Bacterianos , Biofilmes/crescimento & desenvolvimento , Gengiva , Mediadores da Inflamação/imunologia , Monócitos , Mucosa Bucal , Técnicas de Cocultura , Gengiva/imunologia , Gengiva/microbiologia , Gengiva/patologia , Humanos , Inflamação/imunologia , Inflamação/microbiologia , Inflamação/patologia , Monócitos/imunologia , Monócitos/microbiologia , Monócitos/patologia , Mucosa Bucal/imunologia , Mucosa Bucal/microbiologia , Mucosa Bucal/patologia
17.
Int J Med Sci ; 16(10): 1320-1327, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31692996

RESUMO

Porphyromonas gingivalis is a pivotal periodontal pathogen, and the epithelial cells serve as the first physical barrier to defend the host from bacterial attack. Within this host-bacteria interaction, P. gingivalis can modify the host immune reaction and adjust the gene expression, which is associated with periodontitis pathogenesis and developing strategies. Herein, a meta-analysis was made to get the differential gene expression profiles in epithelial cells with or without P. gingivalis infection. The network-based meta-analysis program for gene expression profiling was used. Both the gene ontology analysis and the pathway enrichment analysis of the differentially expressed genes were conducted. Our results determined that 290 genes were consistently up-regulated in P. gingivalis infected epithelial cells. 229 gene ontology biological process terms of up-regulated genes were discovered, including "negative regulation of apoptotic process" and "positive regulation of cell proliferation/migration/angiogenesis". In addition to the well-known inflammatory signaling pathways, the pathway associated with a transcriptional misregulation in cancer has also been increased. Our findings indicated that P. gingivalis benefited from the survival of epithelial cells, and got its success as a colonizer in oral epithelium. The results also suggested that infection of P. gingivalis might contribute to oral cancer through chronic inflammation. Negative regulation of the apoptotic process and transcriptional misregulation in cancer pathway are important contributors to the cellular physiology changes during infection development, which have particular relevance to the pathogenesis and progressions of periodontitis, even to the occurrence of oral cancer.


Assuntos
Infecções por Bacteroidaceae/imunologia , Interações Hospedeiro-Patógeno/genética , Neoplasias Bucais/patologia , Periodontite/imunologia , Porphyromonas gingivalis/imunologia , Infecções por Bacteroidaceae/genética , Infecções por Bacteroidaceae/microbiologia , Infecções por Bacteroidaceae/patologia , Sobrevivência Celular/genética , Sobrevivência Celular/imunologia , Progressão da Doença , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , Perfilação da Expressão Gênica , Ontologia Genética , Gengiva/citologia , Gengiva/imunologia , Gengiva/microbiologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Mucosa Bucal/citologia , Mucosa Bucal/imunologia , Mucosa Bucal/microbiologia , Neoplasias Bucais/genética , Neoplasias Bucais/imunologia , Neoplasias Bucais/microbiologia , Periodontite/genética , Periodontite/microbiologia , Periodontite/patologia , Porphyromonas gingivalis/isolamento & purificação , Porphyromonas gingivalis/patogenicidade , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Regulação para Cima
18.
Nat Commun ; 10(1): 4496, 2019 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-31582750

RESUMO

Solitary chemosensory cells (SCCs) are epithelial sentinels that utilize bitter Tas2r receptors and coupled taste transduction elements to detect pathogenic bacterial metabolites, triggering host defenses to control the infection. Here we report that SCCs are present in mouse gingival junctional epithelium, where they express several Tas2rs and the taste signaling components α-gustducin (Gnat3), TrpM5, and Plcß2. Gnat3-/- mice have altered commensal oral microbiota and accelerated naturally occurring alveolar bone loss. In ligature-induced periodontitis, knockout of taste signaling molecules or genetic absence of gingival SCCs (gSCCs) increases the bacterial load, reduces bacterial diversity, and renders the microbiota more pathogenic, leading to greater alveolar bone loss. Topical treatment with bitter denatonium to activate gSCCs upregulates the expression of antimicrobial peptides and ameliorates ligature-induced periodontitis in wild-type but not in Gnat3-/- mice. We conclude that gSCCs may provide a promising target for treating periodontitis by harnessing innate immunity to regulate the oral microbiome.


Assuntos
Células Quimiorreceptoras/imunologia , Gengiva/imunologia , Imunidade Inata , Microbiota/imunologia , Periodontite/imunologia , Animais , Células Quimiorreceptoras/metabolismo , Modelos Animais de Doenças , Feminino , Gengiva/citologia , Gengiva/microbiologia , Células HEK293 , Proteínas Heterotriméricas de Ligação ao GTP/genética , Proteínas Heterotriméricas de Ligação ao GTP/metabolismo , Humanos , Masculino , Camundongos , Camundongos Knockout , Mucosa Bucal/citologia , Mucosa Bucal/imunologia , Mucosa Bucal/metabolismo , Periodontite/microbiologia , Fosfolipase C beta/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Transdução de Sinais/imunologia , Canais de Cátion TRPM/metabolismo
19.
Am J Clin Dermatol ; 20(6): 847-861, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31313078

RESUMO

Autoimmune bullous diseases are a group of chronic inflammatory disorders caused by autoantibodies targeted against structural proteins of the desmosomal and hemidesmosomal plaques in the skin and mucosa, leading to intra-epithelial or subepithelial blistering. The oral mucosa is frequently affected in these diseases, in particular, in mucous membrane pemphigoid, pemphigus vulgaris, and paraneoplastic pemphigus. The clinical symptoms are heterogeneous and may present with erythema, blisters, erosions, and ulcers localized anywhere on the oral mucosa, and lead to severe complaints for the patients including pain, dysphagia, and foetor. Therefore, a quick and proper diagnosis with adequate treatment is needed. Clinical presentations of autoimmune bullous diseases often overlap and diagnosis cannot be made based on clinical features alone. Immunodiagnostic tests are of great importance in differentiating between the different diseases. Direct immunofluorescence microscopy shows depositions of autoantibodies along the epithelial basement membrane zone in mucous membrane pemphigoid subtypes, or depositions on the epithelial cell surface in pemphigus variants. Additional immunoserological tests are useful to discriminate between the different subtypes of pemphigoid, and are essential to differentiate between pemphigus and paraneoplastic pemphigus. This review gives an overview of the clinical characteristics of oral lesions and the diagnostic procedures in autoimmune blistering diseases, and provides a diagnostic algorithm for daily practice.


Assuntos
Vesícula/diagnóstico , Eritema/diagnóstico , Úlceras Orais/diagnóstico , Penfigoide Bolhoso/diagnóstico , Pênfigo/diagnóstico , Algoritmos , Autoanticorpos/análise , Autoanticorpos/imunologia , Vesícula/imunologia , Vesícula/patologia , Diagnóstico Diferencial , Eritema/imunologia , Eritema/patologia , Humanos , Microscopia de Fluorescência , Mucosa Bucal/imunologia , Mucosa Bucal/patologia , Úlceras Orais/imunologia , Úlceras Orais/patologia , Síndromes Paraneoplásicas/diagnóstico , Síndromes Paraneoplásicas/imunologia , Síndromes Paraneoplásicas/patologia , Penfigoide Bolhoso/complicações , Penfigoide Bolhoso/imunologia , Penfigoide Bolhoso/patologia , Pênfigo/complicações , Pênfigo/imunologia , Pênfigo/patologia
20.
Cell Microbiol ; 21(10): e13078, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31270923

RESUMO

The impact of oral commensal and pathogenic bacteria on peri-implant mucosa is not well understood, despite the high prevalence of peri-implant infections. Hence, we investigated responses of the peri-implant mucosa to Streptococcus oralis or Aggregatibacter actinomycetemcomitans biofilms using a novel in vitro peri-implant mucosa-biofilm model. Our 3D model combined three components, organotypic oral mucosa, implant material, and oral biofilm, with structural assembly close to native situation. S. oralis induced a protective stress response in the peri-implant mucosa through upregulation of heat shock protein (HSP70) genes. Attenuated inflammatory response was indicated by reduced cytokine levels of interleukin-6 (IL-6), interleukin-8 (CXCL8), and monocyte chemoattractant protein-1 (CCL2). The inflammatory balance was preserved through increased levels of tumor necrosis factor-alpha (TNF-α). A. actinomycetemcomitans induced downregulation of genes important for cell survival and host inflammatory response. The reduced cytokine levels of chemokine ligand 1 (CXCL1), CXCL8, and CCL2 also indicated a diminished inflammatory response. The induced immune balance by S. oralis may support oral health, whereas the reduced inflammatory response to A. actinomycetemcomitans may provide colonisation advantage and facilitate later tissue invasion. The comprehensive characterisation of peri-implant mucosa-biofilm interactions using our 3D model can provide new knowledge to improve strategies for prevention and therapy of peri-implant disease.


Assuntos
Aggregatibacter actinomycetemcomitans/fisiologia , Biofilmes/crescimento & desenvolvimento , Modelos Imunológicos , Mucosa Bucal/imunologia , Mucosa Bucal/microbiologia , Peri-Implantite/imunologia , Streptococcus oralis/fisiologia , Aggregatibacter actinomycetemcomitans/patogenicidade , Células Cultivadas , Quimiocina CCL2/metabolismo , Implantes Dentários/efeitos adversos , Implantes Dentários/microbiologia , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Mucosa Bucal/metabolismo , Mucosa Bucal/patologia , Peri-Implantite/microbiologia , Peri-Implantite/patologia , Infecções Relacionadas à Prótese/imunologia , Titânio/química , Fator de Necrose Tumoral alfa/metabolismo
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