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1.
Nature ; 610(7933): 752-760, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36070798

RESUMO

Establishing and maintaining tolerance to self-antigens or innocuous foreign antigens is vital for the preservation of organismal health. Within the thymus, medullary thymic epithelial cells (mTECs) expressing autoimmune regulator (AIRE) have a critical role in self-tolerance through deletion of autoreactive T cells and promotion of thymic regulatory T (Treg) cell development1-4. Within weeks of birth, a separate wave of Treg cell differentiation occurs in the periphery upon exposure to antigens derived from the diet and commensal microbiota5-8, yet the cell types responsible for the generation of peripheral Treg (pTreg) cells have not been identified. Here we describe the identification of a class of RORγt+ antigen-presenting cells called Thetis cells, with transcriptional features of both mTECs and dendritic cells, comprising four major sub-groups (TC I-TC IV). We uncover a developmental wave of Thetis cells within intestinal lymph nodes during a critical window in early life, coinciding with the wave of pTreg cell differentiation. Whereas TC I and TC III expressed the signature mTEC nuclear factor AIRE, TC IV lacked AIRE expression and was enriched for molecules required for pTreg generation, including the TGF-ß-activating integrin αvß8. Loss of either major histocompatibility complex class II (MHCII) or ITGB8 by Thetis cells led to a profound impairment in intestinal pTreg differentiation, with ensuing colitis. By contrast, MHCII expression by RORγt+ group 3 innate lymphoid cells (ILC3) and classical dendritic cells was neither sufficient nor required for pTreg generation, further implicating TC IV as the tolerogenic RORγt+ antigen-presenting cell with an essential function in early life. Our studies reveal parallel pathways for the establishment of tolerance to self and foreign antigens in the thymus and periphery, respectively, marked by the involvement of shared cellular and transcriptional programmes.


Assuntos
Células Apresentadoras de Antígenos , Células Dendríticas , Células Epiteliais , Microbioma Gastrointestinal , Tolerância Imunológica , Linfócitos T Reguladores , Timo , Diferenciação Celular , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Microbioma Gastrointestinal/imunologia , Imunidade Inata , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Timo/citologia , Timo/imunologia , Fator de Crescimento Transformador beta/imunologia , Células Apresentadoras de Antígenos/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia , Linfonodos/imunologia
2.
Front Immunol ; 13: 964910, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059521

RESUMO

Depression in childhood negatively affects the growth and development, school performance, and peer or family relationships of affected children, and may even lead to suicide. Despite this, its etiology and pathophysiology remain largely unknown. Increasing evidence supports that gut microbiota plays a vital role in the development of childhood depression. However, little is known about the underlying mechanisms, as most clinical studies investigating the link between gut microbiota and depression have been undertaken in adult cohorts. In present study, a total of 140 school-aged children (6-12 years) were enrolled, including 92 with depression (male/female: 42/50) and 48 healthy controls (male/female: 22/26) from Lishui, Zhejiang, China. Illumina sequencing of the V3-V4 region of the 16S rRNA gene was used to investigate gut microbiota profiles while Bio-Plex Pro Human Cytokine 27-plex Panel was employed to explore host immune response. We found that, compared with healthy controls, children with depression had greater bacterial richness and altered ß-diversity. Pro-inflammatory genera such as Streptococcus were enriched in the depression group, whereas anti-inflammatory genera such as Faecalibacterium were reduced, as determined by linear discriminant analysis effect size. These changes corresponded to altered bacterial functions, especially the production of immunomodulatory metabolites. We also identified the presence of a complex inflammatory condition in children with depression, characterized by increased levels of pro-inflammatory cytokines such as IL-17 and decreased levels of anti-inflammatory cytokines such as IFN-γ. Correlation analysis demonstrated that the differential cytokine abundance was closely linked to changes in gut microbiota of children with depression. In summary, key functional genera, such as Streptococcus and Faecalibacterium, alone or in combination, could serve as novel and powerful non-invasive biomarkers to distinguish between children with depression from healthy ones. This study was the first to demonstrate that, in Chinese children with depression, gut microbiota homeostasis is disrupted, concomitant with the activation of a complex pro-inflammatory response. These findings suggest that gut microbiota might play an important role in the pathogenesis of depression in school-aged children, while key functional bacteria in gut may serve as novel targets for non-invasive diagnosis and patient-tailored early precise intervention in children with depression.


Assuntos
Citocinas , Depressão , Microbioma Gastrointestinal , Bactérias/genética , Estudos de Casos e Controles , Criança , Citocinas/imunologia , Depressão/imunologia , Depressão/microbiologia , Feminino , Microbioma Gastrointestinal/imunologia , Humanos , Masculino , RNA Ribossômico 16S/genética
3.
Nature ; 610(7933): 737-743, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36071167

RESUMO

The mutualistic relationship of gut-resident microbiota and the host immune system promotes homeostasis that ensures maintenance of the microbial community and of a largely non-aggressive immune cell compartment1,2. The consequences of disturbing this balance include proximal inflammatory conditions, such as Crohn's disease, and systemic illnesses. This equilibrium is achieved in part through the induction of both effector and suppressor arms of the adaptive immune system. Helicobacter species induce T regulatory (Treg) and T follicular helper (TFH) cells under homeostatic conditions, but induce inflammatory T helper 17 (TH17) cells when induced Treg (iTreg) cells are compromised3,4. How Helicobacter and other gut bacteria direct T cells to adopt distinct functions remains poorly understood. Here we investigated the cells and molecular components required for iTreg cell differentiation. We found that antigen presentation by cells expressing RORγt, rather than by classical dendritic cells, was required and sufficient for induction of Treg cells. These RORγt+ cells-probably type 3 innate lymphoid cells and/or Janus cells5-require the antigen-presentation machinery, the chemokine receptor CCR7 and the TGFß activator αv integrin. In the absence of any of these factors, there was expansion of pathogenic TH17 cells instead of iTreg cells, induced by CCR7-independent antigen-presenting cells. Thus, intestinal commensal microbes and their products target multiple antigen-presenting cells with pre-determined features suited to directing appropriate T cell differentiation programmes, rather than a common antigen-presenting cell that they endow with appropriate functions.


Assuntos
Diferenciação Celular , Microbioma Gastrointestinal , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares , Linfócitos T Reguladores , Células Dendríticas/imunologia , Microbioma Gastrointestinal/imunologia , Homeostase , Imunidade Inata , Integrina alfaV/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Receptores CCR7/metabolismo , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Fator de Crescimento Transformador beta/metabolismo , Apresentação de Antígeno/imunologia , Células Apresentadoras de Antígenos/citologia , Células Apresentadoras de Antígenos/imunologia
5.
Science ; 376(6596): 945-950, 2022 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-35617387

RESUMO

Research on newborn immunity has revealed the importance of cell ontogeny, feto-maternal tolerance, and the transfer of maternal antibodies. Less is known about postnatal adaptation to environmental exposures. The microbiome and its importance for health have been extensively studied, but it remains unclear how mutually beneficial relationships between commensal microbes and human cells first arise and are maintained throughout life. Such immune-microbe mutualism, and perturbations thereof, is most likely a root cause of increasing incidences of immune-mediated disorders such as allergies and autoimmunity across many industrialized nations during the past century. In this Review, I discuss our current understanding of immune development and propose that mismatches among ancestral, early-life, and adult environments can explain perturbations to immune-microbe interactions, immune dysregulation, and increased risks of immune-mediated diseases.


Assuntos
Microbioma Gastrointestinal , Interações entre Hospedeiro e Microrganismos , Doenças do Sistema Imunitário , Exposição Ambiental , Microbioma Gastrointestinal/imunologia , Saúde , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Doenças do Sistema Imunitário/imunologia , Doenças do Sistema Imunitário/microbiologia , Recém-Nascido , Simbiose
6.
Food Funct ; 13(11): 6282-6292, 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35607985

RESUMO

The aims of this study were to evaluate whether a diet supplemented with glyceryl butyrate could attenuate the immune-inflammatory response in piglets challenged with enterotoxigenic Escherichia coli (ETEC), and to explore the mechanisms of its regulation. Eighteen weaning piglets were assigned to three diets: basal diet (CON), antibiotics diet (ATB), and 0.5% glyceryl butyrate diet (GB group). Significantly lower concentrations of IL-1ß, IL-6 and TNF-α in the jejunum and IL-6 in the ileum were observed in the GB group than that in the CON group (P < 0.05). Moreover, a decreasing trend of IL-1ß (P = 0.075) and TNF-α (P = 0.070) was observed in the ileum in the GB group. Correspondingly, the GB group had significantly increased mRNA expression of porcine beta defensins (pBDs) in the jejunum (pBD1, pBD2, pBD114 and pBD129) and ileum (pBD2, pBD3, pBD114 and pBD129) (P < 0.05), and protein abundance of Claudin 1, Occludin, and ZO-1 in the jejunum and ileum (P < 0.05). Further research results showed that the improvement of beta defensins and tight junctions in the GB group was related to the decreased phosphorylation of the NFκB/MAPK pathway. In addition, the results of 16S rDNA sequencing showed that glycerol butyrate supplementation altered the ileal microbiota composition of piglets, increasing the relative abundance of Lactobacillus reuteri, Lactobacillus salivarius, and Lactobacillus agrilis. In summary, glyceryl butyrate attenuated the immune-inflammatory response in piglets challenged with ETEC by inhibiting the NF-κB/MAPK pathways and modulating the gut microbiota, and thus improved piglet intestinal health.


Assuntos
Anti-Inflamatórios , Butiratos , Escherichia coli Enterotoxigênica , Infecções por Escherichia coli , Microbioma Gastrointestinal , Intestinos , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Butiratos/farmacologia , Butiratos/uso terapêutico , Escherichia coli Enterotoxigênica/imunologia , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/imunologia , Infecções por Escherichia coli/veterinária , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/imunologia , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/veterinária , Interleucina-6 , Intestinos/efeitos dos fármacos , Intestinos/imunologia , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/imunologia , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , NF-kappa B/imunologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Suínos , Fator de Necrose Tumoral alfa , beta-Defensinas/biossíntese , beta-Defensinas/imunologia
7.
Int J Mol Sci ; 23(5)2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35269795

RESUMO

COVID-19, resulting from the SARS-CoV-2 virus, is a major pandemic that the world is fighting. SARS-CoV-2 primarily causes lung infection by attaching to the ACE2 receptor on the alveolar epithelial cells. However, the ACE2 receptor is also present in intestinal epithelial cells, suggesting a link between nutrition, virulence and clinical outcomes of COVID-19. Respiratory viral infections perturb the gut microbiota. The gut microbiota is shaped by our diet; therefore, a healthy gut is important for optimal metabolism, immunology and protection of the host. Malnutrition causes diverse changes in the immune system by repressing immune responses and enhancing viral vulnerability. Thus, improving gut health with a high-quality, nutrient-filled diet will improve immunity against infections and diseases. This review emphasizes the significance of dietary choices and its subsequent effects on the immune system, which may potentially impact SARS-CoV-2 vulnerability.


Assuntos
COVID-19/imunologia , Comportamento Alimentar , Sistema Imunitário/imunologia , Desnutrição/imunologia , SARS-CoV-2/imunologia , COVID-19/epidemiologia , COVID-19/virologia , Microbioma Gastrointestinal/imunologia , Nível de Saúde , Humanos , Modelos Imunológicos , Estado Nutricional , Pandemias , SARS-CoV-2/patogenicidade , Virulência/imunologia
8.
Vopr Pitan ; 91(1): 86-97, 2022.
Artigo em Russo | MEDLINE | ID: mdl-35298107

RESUMO

The problem of increasing the population antiviral immunity is of particular importance during the third year of the SARS-CoV-2 pandemic. Concomitant intestinal dysbiosis is known to play an significant role in immune cell dysfunction. Therefore, it is very important to take measures to maintain the gut microbiota using the most affordable nutritional remedies, which include fermented milk and probiotic products designed for mass population consumption and capable of enhancing their immune defence when added to the daily diet. The aim of the study was to analyze scientific evidence highlighting the role of intestinal microbiota in maintaining the macro-organism immunological balance, and to evaluate modern fermented milk and probiotic products in terms of their effect on normalising the gut microbiota and their importance in the prevention and treatment of SARS-CoV-2. Material and methods. The presented scientific and analytical review analyzed the data of electronic resources of the Global Health platform, scientific libraries eLIBRARY.RU, Cochrane Library and CyberLeninka, the search system Google Academy¼, specialized sites for scientific publications ScienceDirect and Elsevier, bibliographic databases of articles on medical sciences MEDLINE, CDC infection diseases, Embase and PubMed- NCBI. The structural-logical, analytical and axiomatic methods were used. Results. It has been shown that normal intestinal microbiota takes part in maintaining metabolism in the digestive tract, increases the body's immune reactivity and regulates the functioning of all organs and systems. The severity of dysbiotic disorders can determine susceptibility to SARS-CoV-2, the severity of this infection course, as well as the level of post-infection and post-vaccination anti-COVID-19 immunity. The high prevalence of gut dysbacteriosis indicates the need to strengthen measures of correcting dysbiotic disorders, including the inclusion of fermented and probiotic products in the daily population diet. Conclusion. Fermented milk and probiotic products, as sources of easily digestible macronutrients, essential micronutrients, biologically active substances and beneficial live microorganisms, should be included in the daily diet during the SARS-CoV-2 pandemic to increase the adaptive capacity and immunity of the population.


Assuntos
COVID-19 , Dieta , Microbioma Gastrointestinal , Leite , Probióticos , Animais , COVID-19/imunologia , COVID-19/prevenção & controle , Fermentação , Microbioma Gastrointestinal/imunologia , Humanos , Leite/microbiologia , Pandemias , Probióticos/administração & dosagem , SARS-CoV-2
9.
Int J Mol Sci ; 23(3)2022 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-35163417

RESUMO

Some say that all diseases begin in the gut. Interestingly, this concept is actually quite old, since it is attributed to the Ancient Greek physician Hippocrates, who proposed the hypothesis nearly 2500 years ago. The continuous breakthroughs in modern medicine have transformed our classic understanding of the gastrointestinal tract (GIT) and human health. Although the gut microbiota (GMB) has proven to be a core component of human health under standard metabolic conditions, there is now also a strong link connecting the composition and function of the GMB to the development of numerous diseases, especially the ones of musculoskeletal nature. The symbiotic microbes that reside in the gastrointestinal tract are very sensitive to biochemical stimuli and may respond in many different ways depending on the nature of these biological signals. Certain variables such as nutrition and physical modulation can either enhance or disrupt the equilibrium between the various species of gut microbes. In fact, fat-rich diets can cause dysbiosis, which decreases the number of protective bacteria and compromises the integrity of the epithelial barrier in the GIT. Overgrowth of pathogenic microbes then release higher quantities of toxic metabolites into the circulatory system, especially the pro-inflammatory cytokines detected in osteoarthritis (OA), thereby promoting inflammation and the initiation of many disease processes throughout the body. Although many studies link OA with GMB perturbations, further research is still needed.


Assuntos
Disbiose , Microbioma Gastrointestinal/imunologia , Mucosa Intestinal , Osteoartrite , Animais , Disbiose/imunologia , Disbiose/microbiologia , Humanos , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Osteoartrite/etiologia , Osteoartrite/imunologia , Osteoartrite/microbiologia
10.
J Exp Med ; 219(3)2022 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-35195681

RESUMO

The gastrointestinal tract contains trillions of microorganisms that exist symbiotically with the host due to a tolerant, regulatory cell-rich intestinal immune system. However, this intimate relationship with the microbiome inevitably comes with risks, with intestinal organisms being the most common cause of bacteremia. The vasculature of the brain-lining meninges contains fenestrated endothelium, conferring vulnerability to invasion by circulating microbes. We propose that this has evolutionarily led to close links between gut and meningeal immunity, to prime the central nervous system defense against the most likely invaders. This paradigm is exemplified by the dural venous sinus IgA defense system, where the antibody repertoire mirrors that of the gut.


Assuntos
Trato Gastrointestinal/imunologia , Meninges/imunologia , Animais , Microbioma Gastrointestinal/imunologia , Humanos , Imunoglobulina A/imunologia , Meninges/microbiologia , Modelos Imunológicos , Plasmócitos/imunologia
11.
Front Immunol ; 13: 773341, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35185877

RESUMO

The herpes virus entry mediator (HVEM) is an immune checkpoint molecule regulating immune response, but its role in tissue repair remains unclear. Here, we reported that HVEM deficiency aggravated hepatobiliary damage and compromised liver repair after 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced injury. A similar phenotype was observed in B and T lymphocyte attenuator (BTLA)-deficient mice. These were correlated with impairment of neutrophil accumulation in the liver after injury. The hepatic neutrophil accumulation was regulated by microbial-derived secondary bile acids. HVEM-deficient mice had reduced ability to deconjugate bile acids during DDC-feeding, suggesting a gut microbiota defect. Consistently, both HVEM and BTLA deficiency had dysregulated intestinal IgA responses targeting the gut microbes. These results suggest that the HVEM-BTLA signaling may restrain liver injury by regulating the gut microbiota.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas/imunologia , Microbioma Gastrointestinal/imunologia , Receptores Imunológicos/imunologia , Membro 14 de Receptores do Fator de Necrose Tumoral/imunologia , Transdução de Sinais/imunologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Piridinas/toxicidade , Receptores Imunológicos/deficiência , Membro 14 de Receptores do Fator de Necrose Tumoral/deficiência
13.
J Integr Neurosci ; 21(1): 9, 2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35164445

RESUMO

Epilepsy is one of the most common neurology diseases. It is characterized by recurrent, spontaneous seizures and accompanied by various comorbidities which can significantly affect a person's life. Accumulating evidence indicates an essential pathophysiological role for neuroinflammation in epilepsy, which involves activation of microglia and astrocytes, recruitment of peripheral leukocytes into the central nervous system, and release of some inflammatory mediators, including pro-inflammatory factors and anti-inflammatory cytokines. There is complex crosstalk between the central nervous system and peripheral immune responses associated with the progression of epilepsy. This review provides an update of current knowledge about the contribution of this crosstalk associated with epilepsy. Additionally, how gut microbiota is involved in epilepsy and its possible influence on crosstalk is also discussed. Such recent advances in understanding suggest innovative methods for targeting the molecules correlated with the crosstalk and may provide a better prognosis for patients diagnosed with epilepsy.


Assuntos
Barreira Hematoencefálica/imunologia , Epilepsia/imunologia , Microbioma Gastrointestinal/imunologia , Sistema Imunitário/imunologia , /imunologia , Animais , Humanos
14.
PLoS One ; 17(2): e0261103, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35196314

RESUMO

A variety of islet autoantibodies (AAbs) can predict and possibly dictate eventual type 1 diabetes (T1D) diagnosis. Upwards of 75% of those with T1D are positive for AAbs against glutamic acid decarboxylase (GAD65 or GAD), a producer of gamma-aminobutyric acid (GABA) in human pancreatic beta cells. Interestingly, bacterial populations within the human gut also express GAD and produce GABA. Evidence suggests that dysbiosis of the microbiome may correlate with T1D pathogenesis and physiology. Therefore, autoimmune linkages between the gut microbiome and islets susceptible to autoimmune attack need to be further elucidated. Utilizing in silico analyses, we show that 25 GAD sequences from human gut bacterial sources show sequence and motif similarities to human beta cell GAD65. Our motif analyses determined that most gut GAD sequences contain the pyroxical dependent decarboxylase (PDD) domain of human GAD65, which is important for its enzymatic activity. Additionally, we showed overlap with known human GAD65 T cell receptor epitopes, which may implicate the immune destruction of beta cells. Thus, we propose a physiological hypothesis in which changes in the gut microbiome in those with T1D result in a release of bacterial GAD, thus causing miseducation of the host immune system. Due to the notable similarities we found between human and bacterial GAD, these deputized immune cells may then target human beta cells leading to the development of T1D.


Assuntos
Autoanticorpos/imunologia , Bactérias/enzimologia , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/microbiologia , Microbioma Gastrointestinal/imunologia , Glutamato Descarboxilase/genética , Glutamato Descarboxilase/imunologia , Animais , Células Apresentadoras de Antígenos/imunologia , Simulação por Computador , Diabetes Mellitus Tipo 1/enzimologia , Epitopos de Linfócito T/imunologia , Genes Bacterianos , Humanos , Ilhotas Pancreáticas/enzimologia , Ilhotas Pancreáticas/imunologia , Camundongos , Pan troglodytes/microbiologia , Filogenia , Domínios Proteicos , Alinhamento de Sequência/métodos , Ácido gama-Aminobutírico/metabolismo
15.
Immunity ; 55(2): 192-194, 2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35139348

RESUMO

The microbiome affects establishment and growth of tumors as well as response to immune-based therapies. In this issue of Immunity, Hezaveh et al. (2022) reveal that metabolites of dietary tryptophan generated by the gut microbiota activate the aryl hydrocarbon receptor in myeloid cells, promoting an immune suppressive tumor microenvironment and facilitating pancreatic ductal adenocarcinoma growth.


Assuntos
Microbioma Gastrointestinal , Microbiota , Neoplasias , Microbioma Gastrointestinal/imunologia , Humanos , Receptores de Hidrocarboneto Arílico/metabolismo , Triptofano/metabolismo , Microambiente Tumoral
17.
Nutrients ; 14(2)2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35057528

RESUMO

Gut bacteria release extracellular vesicles (BEVs) as an intercellular communication mechanism that primes the host innate immune system. BEVs from E. coli activate dendritic cells (DCs) and subsequent T-cell responses in a strain-specific manner. The specific immunomodulatory effects were, in part, mediated by differential regulation of miRNAs. This study aimed to deepen understanding of the mechanisms of BEVs to drive specific immune responses by analyzing their impact on DC-secreted cytokines and exosomes. DCs were challenged with BEVs from probiotic and commensal E. coli strains. The ability of DC-secreted factors to activate T-cell responses was assessed by cytokine quantification in indirect DCs/naïve CD4+ T-cells co-cultures on Transwell supports. DC-exosomes were characterized in terms of costimulatory molecules and miRNAs cargo. In the absence of direct cellular contacts, DC-secreted factors triggered secretion of effector cytokines by T-cells with the same trend as direct DC/T-cell co-cultures. The main differences between the strains influenced the production of Th1- and Treg-specific cytokines. Exosomes released by BEV-activated DCs were enriched in surface proteins involved in antigen presentation and T-cell activation, but differed in the content of immune-related miRNA, depending on the origin of the BEVs. These differences were consistent with the derived immune responses.


Assuntos
Citocinas/metabolismo , Células Dendríticas/microbiologia , Exossomos/microbiologia , Vesículas Extracelulares/imunologia , Microbioma Gastrointestinal/imunologia , Apresentação de Antígeno , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/microbiologia , Comunicação Celular/imunologia , Técnicas de Cocultura , Escherichia coli/imunologia , Exossomos/imunologia , Humanos , Ativação Linfocitária/imunologia , MicroRNAs/metabolismo , Probióticos/administração & dosagem , Linfócitos T/imunologia , Linfócitos T/microbiologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/microbiologia
18.
Nurs Res ; 71(1): 43-53, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34985847

RESUMO

BACKGROUND: Nurse researchers are well poised to study the connection of the microbiome to health and disease. Evaluating published microbiome results can assist with study design and hypothesis generation. OBJECTIVES: This article aims to present and define important analysis considerations in microbiome study planning and to identify genera shared across studies despite methodological differences. This methods article will highlight a workflow that the nurse scientist can use to combine and evaluate taxonomy tables for microbiome study or research proposal planning. METHODS: We compiled taxonomy tables from 13 published gut microbiome studies that had used Ion Torrent sequencing technology. We searched for studies that had amplified multiple hypervariable (V) regions of the 16S rRNA gene when sequencing the bacteria from healthy gut samples. RESULTS: We obtained 15 taxonomy tables from the 13 studies, comprised of samples from four continents and eight V regions. Methodology among studies was highly variable, including differences in V regions amplified, geographic location, and population demographics. Nevertheless, of the 354 total genera identified from the 15 data sets, 25 were shared in all V regions and the four continents. When relative abundance differences across the V regions were compared, Dorea and Roseburia were statistically different. Taxonomy tables from Asian subjects had increased average abundances of Prevotella and lowered abundances of Bacteroides compared with the European, North American, and South American study subjects. DISCUSSION: Evaluating taxonomy tables from previously published literature is essential for study planning. The genera found from different V regions and continents highlight geography and V region as important variables to consider in microbiome study design. The 25 shared genera across the various studies may represent genera commonly found in healthy gut microbiomes. Understanding the factors that may affect the results from a variety of microbiome studies will allow nurse scientists to plan research proposals in an informed manner. This work presents a valuable framework for future cross-study comparisons conducted across the globe.


Assuntos
Classificação/métodos , Microbioma Gastrointestinal/fisiologia , Microbioma Gastrointestinal/imunologia , Saúde Global/estatística & dados numéricos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Sequenciamento de Nucleotídeos em Larga Escala/estatística & dados numéricos , Humanos , Análise de Sequência de DNA/métodos , Análise de Sequência de DNA/estatística & dados numéricos
19.
JCI Insight ; 7(4)2022 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-35077397

RESUMO

Commensal microbes critically regulate skeletal homeostasis, yet the impact of specific microbiota communities on osteoimmune response mechanisms is unknown. To discern osteoimmunomodulatory effects imparted by the commensal oral microbiota that are distinct from the systemic microbiota, osteoimmunology studies were performed in both alveolar bone and nonoral skeletal sites of specific pathogen-free (SPF) versus germ-free (GF) mice and SPF mice subjected to saline versus chlorhexidine oral rinses. SPF versus GF mice had reduced cortical/trabecular bone and an enhanced pro-osteoclastic phenotype in alveolar bone. TLR signaling and Th17 cells that have known pro-osteoclastic actions were increased in alveolar BM, but not long BM, of SPF versus GF mice. MHC II antigen presentation genes and activated DCs and CD4+ T cells were elevated in alveolar BM, but not long BM, of SPF versus GF mice. These findings were substantiated by in vitro allostimulation studies demonstrating increased activated DCs derived from alveolar BM, but not long BM, of SPF versus GF mice. Chlorhexidine antiseptic rinse depleted the oral, but not gut, bacteriome in SPF mice. Findings from saline- versus chlorhexidine-treated SPF mice corroborated outcomes from SPF versus GF mice, which reveals that the commensal oral microbiota imparts osteoimmunomodulatory effects separate from the systemic microbiome.


Assuntos
Microbioma Gastrointestinal/imunologia , Vida Livre de Germes/imunologia , Boca/microbiologia , Osteoclastos/imunologia , Organismos Livres de Patógenos Específicos/imunologia , Animais , Homeostase/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais
20.
Int J Mol Sci ; 23(2)2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35054989

RESUMO

Phenotyping cardiovascular illness and recognising heterogeneities within are pivotal in the contemporary era. Besides traditional risk factors, accumulated evidence suggested that a high inflammatory burden has emerged as a key characteristic modulating both the pathogenesis and progression of cardiovascular diseases, inclusive of atherosclerosis and myocardial infarction. To mechanistically elucidate the correlation, signalling pathways downstream to Toll-like receptors, nucleotide oligomerisation domain-like receptors, interleukins, tumour necrosis factor, and corresponding cytokines were raised as central mechanisms exerting the effect of inflammation. Other remarkable adjuvant factors include oxidative stress and secondary ferroptosis. These molecular discoveries have propelled pharmaceutical advancements. Statin was suggested to confer cardiovascular benefits not only by lowering cholesterol levels but also by attenuating inflammation. Colchicine was repurposed as an immunomodulator co-administered with coronary intervention. Novel interleukin-1ß and -6 antagonists exhibited promising cardiac benefits in the recent trials as well. Moreover, manipulation of gut microbiota and associated metabolites was addressed to antagonise inflammation-related cardiovascular pathophysiology. The gut-cardio-renal axis was therein established to explain the mutual interrelationship. As for future perspectives, artificial intelligence in conjunction with machine learning could better elucidate the sequencing of the microbiome and data mining. Comprehensively understanding the interplay between the gut microbiome and its cardiovascular impact will help identify future therapeutic targets, affording holistic care for patients with cardiovascular diseases.


Assuntos
Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/terapia , Suscetibilidade a Doenças , Imunomodulação , Imunoterapia , Inflamação/complicações , Animais , Biomarcadores , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/metabolismo , Gerenciamento Clínico , Suscetibilidade a Doenças/imunologia , Retroalimentação Fisiológica , Microbioma Gastrointestinal/imunologia , Humanos , Imunomodulação/efeitos dos fármacos , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Nefropatias/complicações , Nefropatias/etiologia , Terapia de Alvo Molecular , Fatores de Risco , Resultado do Tratamento
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