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1.
Bull Exp Biol Med ; 170(4): 458-460, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33713222

RESUMO

High biofilm-forming capacity of Staphylococcus spp. strains isolated from biomaterial of patients with infectious complications after primary knee replacement developed within 6-12 months after surgery was experimentally demonstrated. Differential leukocyte counts and some indicators of cell immunity in these patients were compared with those in patients without purulent complications and healthy volunteers. In patients with implant-associated infection, the relative numbers of T cells (both T-helpers and T-suppressors) B cells were significantly (p<0.05) reduced, while the number of NK cells was significantly increased in comparison with the corresponding parameters in other groups. The revealed changes attest to cell immunity failure in biofilm infection.


Assuntos
Biofilmes , Imunidade Celular/fisiologia , Linfócitos B/metabolismo , Voluntários Saudáveis , Humanos , Staphylococcus/imunologia , Staphylococcus/fisiologia , Staphylococcus epidermidis/imunologia , Staphylococcus epidermidis/fisiologia
2.
Nature ; 590(7847): 624-629, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33461211

RESUMO

In the type III CRISPR-Cas immune response of prokaryotes, infection triggers the production of cyclic oligoadenylates that bind and activate proteins that contain a CARF domain1,2. Many type III loci are associated with proteins in which the CRISPR-associated Rossman fold (CARF) domain is fused to a restriction  endonuclease-like domain3,4. However, with the exception of the well-characterized Csm6 and Csx1 ribonucleases5,6, whether and how these inducible effectors provide defence is not known. Here we investigated a type III CRISPR accessory protein, which we name cyclic-oligoadenylate-activated single-stranded ribonuclease and single-stranded deoxyribonuclease 1 (Card1). Card1 forms a symmetrical dimer that has a large central cavity between its CRISPR-associated Rossmann fold and restriction endonuclease domains that binds cyclic tetra-adenylate. The binding of ligand results in a conformational change comprising the rotation of individual monomers relative to each other to form a more compact dimeric scaffold, in which a manganese cation coordinates the catalytic residues and activates the cleavage of single-stranded-but not double-stranded-nucleic acids (both DNA and RNA). In vivo, activation of Card1 induces dormancy of the infected hosts to provide immunity against phage infection and plasmids. Our results highlight the diversity of strategies used in CRISPR systems to provide immunity.


Assuntos
Nucleotídeos de Adenina/metabolismo , Sistemas CRISPR-Cas/imunologia , DNA de Cadeia Simples/metabolismo , Desoxirribonucleases/metabolismo , Endorribonucleases/metabolismo , Oligorribonucleotídeos/metabolismo , RNA/metabolismo , Staphylococcus/enzimologia , Staphylococcus/imunologia , Nucleotídeos de Adenina/imunologia , Trifosfato de Adenosina/metabolismo , Bacteriófagos/imunologia , Bacteriófagos/fisiologia , Biocatálise , Domínio Catalítico , Desoxirribonucleases/química , Desoxirribonucleases/genética , Endorribonucleases/química , Endorribonucleases/genética , Ativação Enzimática , Ligantes , Manganês/química , Manganês/metabolismo , Modelos Moleculares , Oligorribonucleotídeos/imunologia , Plasmídeos/genética , Plasmídeos/metabolismo , Multimerização Proteica , Rotação , Staphylococcus/crescimento & desenvolvimento , Staphylococcus/virologia , Especificidade por Substrato
4.
Benef Microbes ; 11(6): 561-572, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33032469

RESUMO

The use of antibiotics to prevent bovine mastitis is responsible for the emergence and selection of resistant strains. Lactic acid bacteria (LAB) could be introduced into animal feed as an alternative prevention method that would bypass the risk of resistance development. In previous research, we demonstrated that two probiotic LAB strains isolated from bovine milk were capable of stimulating the production of antibodies and the host's immune cellular response in the udder. The present study aimed to elucidate whether the antibodies of animals inoculated with these strains were able to increase phagocytosis by neutrophils and inhibit the growth of different mastitis-causing pathogens. Moreover, the effect of LAB on the expression of pro-inflammatory cytokines was assessed. Ten animals were inoculated intramammarily with 106 cells of the two strains at dry-off. The blood serum was tested for its ability to opsonize bovine mastitis pathogens, the in vitro bactericidal activity of bovine blood and milk against these pathogens was determined, and cytokine mRNA expression was quantified in milk somatic cells. The inoculated animals did not show abnormal signs of sensitivity to the LAB. Their blood serum significantly enhanced the phagocytosis of Staphylococcus spp. and the LAB. Escherichia coli and Streptococcus uberis were inhibited by the milk serum but not the blood serum, whereas Staphylococcus aureus and Staphylococcus haemolyticus were inhibited by both. In regard to cytokine expression, interleukin (IL)-1ß increased markedly for up to 4 h post-inoculation, and an increase in IL-8 was observed 4, 12 and 24 h after inoculation. Tumour necrosis factor-α mRNA increased 1 and 2 h after inoculation and a significant difference was registered at 6 h for interferon-γ. This rapid immunomodulatory response shows that inoculating animals with LAB at dry-off, when they are especially susceptible, could be a useful strategy for the prevention of bovine mastitis.


Assuntos
Anticorpos Antibacterianos/imunologia , Bovinos/imunologia , Lactobacillales , Glândulas Mamárias Animais/imunologia , Mastite Bovina/prevenção & controle , Probióticos , Animais , Anticorpos Antibacterianos/sangue , Atividade Bactericida do Sangue , Bovinos/microbiologia , Citocinas/genética , Citocinas/metabolismo , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/imunologia , Feminino , Lactobacillales/imunologia , Glândulas Mamárias Animais/microbiologia , Mastite Bovina/imunologia , Mastite Bovina/microbiologia , Leite/imunologia , Leite/metabolismo , Neutrófilos/imunologia , Fagocitose , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Staphylococcus/crescimento & desenvolvimento , Staphylococcus/imunologia , Streptococcus/crescimento & desenvolvimento , Streptococcus/imunologia
5.
Int J Mol Sci ; 21(17)2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32872360

RESUMO

Staphylococcus argenteus is an emerging species responsible for infections comparable to those induced by Staphylococcus aureus. It has been involved in few chronic or persistent infections so far. In this study, we described a case of a persistent prosthetic-joint infection (PJI) affecting a young woman. We investigated in vitro the virulence traits of the incriminated S. argenteus strain (bone cell invasion, biofilm formation and induction of inflammation) and analyzed its genome, in comparison with two other strains of S. argenteus and two S. aureus isolates. It appeared that this S. argenteus PJI strain combined biofilm formation, osteoblast invasion and intracellular persistence abilities together with genes potentially involved in the escape of the host immune defenses, which might explain the chronicization of the infection.


Assuntos
Infecções Relacionadas à Prótese/microbiologia , Infecções Estafilocócicas/diagnóstico , Staphylococcus/patogenicidade , Fatores de Virulência/genética , Sequenciamento Completo do Genoma/métodos , Proteínas de Bactérias/genética , Biofilmes/crescimento & desenvolvimento , Linhagem Celular , Feminino , Humanos , Evasão da Resposta Imune , Osteoblastos/citologia , Osteoblastos/microbiologia , Infecções Relacionadas à Prótese/imunologia , Infecções Estafilocócicas/imunologia , Staphylococcus/imunologia , Staphylococcus/isolamento & purificação , Adulto Jovem
6.
Front Immunol ; 11: 1639, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32849560

RESUMO

Staphylococcus aureus is a notorious bacterial pathogen that often causes soft tissue and bloodstream infections and invariably garners resistance mechanisms against new antibiotics. Modulation of the host immune response by metabolites is a powerful tool against bacterial infections, but has not yet been used against S. aureus infections. In this study, we identified four metabolite biomarkers: L-proline, L-isoleucine, L-leucine, and L-valine (PILV), through a metabolomics study using animal models of S. aureus bloodstream infection. The exogenous administration of each metabolite or of PILV showed anti-infective effects, and a higher protection was achieved with PILV in comparison to individual metabolites. During the staphylococcal infection, the expression of most host arginase and nitric oxide synthase (NOS) isozymes was simultaneously induced in mouse liver, kidney, and blood samples. However, the induction of arginase isozymes was dramatically stronger than that of NOS isozymes. This elevated arginase activity was inhibited by the metabolite biomarkers thus killing S. aureus, and PILV exhibited the strongest inhibition of arginase activity and bacterial inhibition. The suppression of arginase activity also contributed to the metabolite-mediated phagocytic killing of S. aureus in mouse and human blood. Our findings demonstrate the metabolite-mediated arginase inhibition as a therapeutic intervention for S. aureus infection.


Assuntos
Arginase/metabolismo , Interações Hospedeiro-Patógeno , Metaboloma , Sepse/imunologia , Sepse/metabolismo , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/metabolismo , Animais , Biomarcadores , Biópsia , Biologia Computacional , Modelos Animais de Doenças , Ativação Enzimática , Feminino , Interações Hospedeiro-Patógeno/imunologia , Humanos , Metabolômica , Camundongos , Óxido Nítrico/metabolismo , Fagócitos/imunologia , Fagócitos/metabolismo , Prognóstico , Células RAW 264.7 , Sepse/mortalidade , Sepse/patologia , Infecções Estafilocócicas/mortalidade , Infecções Estafilocócicas/patologia , Staphylococcus/imunologia , Staphylococcus aureus/imunologia
7.
Clin Orthop Relat Res ; 478(12): 2786-2797, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32667753

RESUMO

BACKGROUND: Preoperative synovial fluid culture is pivotal in the early diagnosis of prosthetic joint infection (PJI) but may yield false-positive and false-negative results. We evaluated the predictive value of synovial fluid culture results combined with the measurement of serum anti-staphylococcal antibodies (SASA). QUESTIONS/PURPOSES: (1) For hip and knee PJI, does combining positive SASA results with preoperative synovial culture results improve the positive predictive value (PPV) of preoperative synovial fluid culture alone? (2) Does combining preoperative synovial fluid culture results with a positive cell count and differential result increase the PPV of preoperative synovial fluid culture alone? (3) What proportion of isolated organisms exhibit concordance in antibiotic susceptibility: preoperative aspiration versus intraoperative isolates? METHODS: A prospective study was conducted at two French reference centers that manage bone and joint infections and included 481 adult patients who had a revision or resection arthroplasty between June 25, 2012 and June 23, 2014. Exclusion criteria including no serum sample available for immunoassay, the lack of microbiological documentation, and the absence of preoperative aspiration reduced the patient number to 353. Seven patients with an undetermined SASA result were excluded from the analysis. We also excluded patients with PJI involving more than one Staphylococcus species (polystaphylococcal infection) and those in whom more than one Staphylococcus species was recovered from the preoperative synovial fluid culture (polystaphylococcal synovial fluid culture). In total, 340 patients were included in the analysis (no infection, 67% [226 of 340]; staphylococcal infection, 21% [71 of 340]; other infection, 13% [43 of 340]). The preoperative synovial fluid analysis included a cell count and differential and bacterial culture. SASAs were measured using a multiplex immunoassay. The diagnosis of PJI was determined using the Infectious Diseases Society of America (IDSA) criteria [] and intraoperative tissue culture at the time of revision surgery was used as the gold standard (at least one positive intraoperative sample for a "virulent" organism (such as S. aureus) or two positive samples for a "non-virulent" (for example S. epidermidis). RESULTS: SASA increased the PPV compared with synovial fluid culture alone (92% [95% CI 82 to 97] versus 79% [95% CI 68 to 87]; p = 0.04); when stratified by site, an increase in PPV was seen in hip infections (100% [95% CI 89 to 100] versus 77% [95% CI 63 to 88]; p = 0.01) but not in knee infections (84% [95% CI 66 to 95] versus 80% [95% CI 64 to 91]; p = 0.75). A positive cell count and differential result increased the PPV of staphylococcal synovial fluid cultures compared with synovial fluid culture alone (86% [95% CI 70 to 95] versus 79% [95% CI 68 to 87]; p = 0.36); when stratified by site, no difference in hip and knee infections was observed (86% [95% CI 67 to 96] versus 77% [95% CI 63 to 88]; p = 0.42) and 86% [95% CI 70 to 95] versus 80% [95% CI 64 to 91]; p = 0.74). CONCLUSION: SASA measurement improves the predictive value of synovial fluid cultures of the hip for all staphylococcal organisms, including coagulase-negative staphylococci, but the PPV of SASA plus synovial fluid culture it is not superior to the PPV of synovial fluid cell count/differential plus synovial culture for the knee. LEVEL OF EVIDENCE: Level III, diagnostic study.


Assuntos
Anticorpos Antibacterianos/sangue , Artroplastia de Quadril/efeitos adversos , Prótese de Quadril/efeitos adversos , Infecções Relacionadas à Prótese/diagnóstico , Testes Sorológicos , Infecções Estafilocócicas/diagnóstico , Staphylococcus/imunologia , Líquido Sinovial/microbiologia , Idoso , Artroplastia de Quadril/instrumentação , Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/instrumentação , Biomarcadores/sangue , Feminino , França , Humanos , Prótese do Joelho/efeitos adversos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Cuidados Pré-Operatórios , Estudos Prospectivos , Infecções Relacionadas à Prótese/sangue , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/cirurgia , Reprodutibilidade dos Testes , Infecções Estafilocócicas/sangue , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/cirurgia , Sucção
8.
Nat Commun ; 11(1): 1539, 2020 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-32210242

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a chronic and fatal disease of unknown etiology; however, apoptosis of lung alveolar epithelial cells plays a role in disease progression. This intractable disease is associated with increased abundance of Staphylococcus and Streptococcus in the lungs, yet their roles in disease pathogenesis remain elusive. Here, we report that Staphylococcus nepalensis releases corisin, a peptide conserved in diverse staphylococci, to induce apoptosis of lung epithelial cells. The disease in mice exhibits acute exacerbation after intrapulmonary instillation of corisin or after lung infection with corisin-harboring S. nepalensis compared to untreated mice or mice infected with bacteria lacking corisin. Correspondingly, the lung corisin levels are significantly increased in human IPF patients with acute exacerbation compared to patients without disease exacerbation. Our results suggest that bacteria shedding corisin are involved in acute exacerbation of IPF, yielding insights to the molecular basis for the elevation of staphylococci in pulmonary fibrosis.


Assuntos
Proteínas Reguladoras de Apoptose/imunologia , Proteínas de Bactérias/imunologia , Fibrose Pulmonar Idiopática/imunologia , Peptídeos/imunologia , Staphylococcus/imunologia , Idoso , Animais , Apoptose/imunologia , Proteínas Reguladoras de Apoptose/análise , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas de Bactérias/análise , Proteínas de Bactérias/metabolismo , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/imunologia , Modelos Animais de Doenças , Células Epiteliais/imunologia , Células Epiteliais/patologia , Feminino , Voluntários Saudáveis , Humanos , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/microbiologia , Fibrose Pulmonar Idiopática/patologia , Pulmão/imunologia , Pulmão/microbiologia , Pulmão/patologia , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Transgênicos , Peptídeos/análise , Peptídeos/metabolismo , Staphylococcus/metabolismo , Staphylococcus/patogenicidade , Exacerbação dos Sintomas , Linfócitos T Reguladores/imunologia , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/imunologia
9.
Dermatitis ; 31(3): 215-222, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32209872

RESUMO

BACKGROUND: Skin colonization by Staphylococcus aureus (SA) correlates with increased severity of atopic dermatitis (AD). The role of nasal SA carriage and coagulase-negative staphylococci (CNSs) in AD is unclear. OBJECTIVE: The aim of this study was to assess the influence of colonization of lesional/nonlesional skin and the anterior nares by SA and CNSs on AD severity in 63 adult patients. METHODS: Disease severity was assessed with SCORAD index. The total immunoglobulin E (IgE) concentration was determined using the enzyme-linked immunosorbent assay method. The prevalence and abundance of staphylococci were assessed with the combination of bacterial culture and mass spectrometry. RESULTS: The prevalence values of SA within the skin (lesional/nonlesional) and anterior nares were 79.4%/61.9% and 69.8%, respectively (vs 5.6% and 13.9%, respectively in controls, P < 0.0001). The carriage of CNSs in all niches was associated with lower mean IgE concentration (1164.66 ± 1010.36 vs 1762.99 ± 1059.15, P < 0.0213; 1166.9 ± 1006.4 vs 2152.7 ± 759.2, P < 0.0063; 1022 ± 1100 vs 1925 ± 880.8, P < 0.0044, respectively). The abundance of SA correlated with the extent of skin lesions and total IgE (ρ = 0.42, P = 0.0007; ρ = 0.488, P < 0.0001; ρ = 0.312, P < 0.2; and ρ = 0.402, P = 0.0007; ρ = 0.403, P < 0.002; ρ = 0.287, P < 0.03, respectively). CONCLUSIONS: Atopic dermatitis severity correlates with both cutaneous and nasal colonization by SA. Staphylococcus aureus seems to promote TH2-type response, whereas CNS probably limits this process. Preventive measures within the anterior nares should be considered for AD patients.


Assuntos
Infecções Assintomáticas , Carga Bacteriana , Dermatite Atópica/fisiopatologia , Mucosa Nasal/microbiologia , Staphylococcus aureus/isolamento & purificação , Adolescente , Adulto , Idoso , Dermatite Atópica/imunologia , Feminino , Humanos , Imunoglobulina E/imunologia , Masculino , Pessoa de Meia-Idade , Polônia , Índice de Gravidade de Doença , Staphylococcus/imunologia , Staphylococcus/isolamento & purificação , Staphylococcus aureus/imunologia , Adulto Jovem
10.
Sci Rep ; 10(1): 2024, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32029783

RESUMO

The transmembrane protein claudin-1 is a major component of epidermal tight junctions (TJs), which create a dynamic paracellular barrier in the epidermis. Claudin-1 downregulation has been linked to atopic dermatitis (AD) pathogenesis but variable levels of claudin-1 have also been observed in healthy skin. To elucidate the impact of different levels of claudin-1 in healthy and diseased skin we determined claudin-1 levels in AD patients and controls and correlated them to TJ and skin barrier function. We observed a strikingly broad range of claudin-1 levels with stable TJ and overall skin barrier function in healthy and non-lesional skin. However, a significant decrease in TJ barrier function was detected in lesional AD skin where claudin-1 levels were further reduced. Investigations on reconstructed human epidermis expressing different levels of claudin-1 revealed that claudin-1 levels correlated with inside-out and outside-in barrier function, with a higher coherence for smaller molecular tracers. Claudin-1 decrease induced keratinocyte-autonomous IL-1ß expression and fostered inflammatory epidermal responses to non-pathogenic Staphylococci. In conclusion, claudin-1 decrease beyond a threshold level results in TJ and epidermal barrier function impairment and induces inflammation in human epidermis. Increasing claudin-1 levels might improve barrier function and decrease inflammation and therefore be a target for AD treatment.


Assuntos
Claudina-1/metabolismo , Dermatite Atópica/imunologia , Epiderme/patologia , Junções Íntimas/patologia , Adulto , Biópsia , Estudos de Casos e Controles , Células Cultivadas , Claudina-1/análise , Claudina-1/genética , Dermatite Atópica/microbiologia , Dermatite Atópica/patologia , Regulação para Baixo , Epiderme/imunologia , Epiderme/microbiologia , Feminino , Técnicas de Silenciamento de Genes , Voluntários Saudáveis , Humanos , Interleucina-1beta/metabolismo , Queratinócitos/imunologia , Queratinócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Cultura Primária de Células , Staphylococcus/imunologia , Staphylococcus/isolamento & purificação , Perda Insensível de Água/imunologia , Adulto Jovem
11.
Am J Clin Dermatol ; 21(3): 355-370, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32008176

RESUMO

Palmoplantar pustulosis (PPP) is a chronic, recurrent skin disease belonging to the spectrum of psoriasis. It is characterized by an eruption of sterile pustules on the palms and soles. Recent studies in PPP have focused on genetic differences between pustular phenotypes and the role of the innate immunological system and the microbiome in the etiopathogenesis of the disease. Mutations in IL36RN (a major predisposing factor for generalized pustular psoriasis) were found in selected patients with PPP and were associated with earlier disease onset. Studies have shown that the interleukin (IL)-17 and IL-36 pathways might be involved in the pathogenesis of PPP. A microbiome has been demonstrated in the vesicopustules of PPP, and an abundance of Staphylococcus appears to be increased by smoking. Improved understanding of the underlying etiopathogenesis of PPP has led to advances in treatment options, and targeted therapies for PPP have been evaluated or are under evaluation against more than 12 molecules in ongoing clinical trials. These targets include CXCR2 (IL-8 receptor type B), granulocyte colony-stimulating factor receptor, IL-1 receptor, IL-8, IL-12, IL-23, IL-17A, IL-17 receptor, IL-36 receptor, phosphodiesterase-4, and tumor necrosis factor-α.


Assuntos
Citocinas/genética , Fármacos Dermatológicos/uso terapêutico , Microbiota/imunologia , Psoríase/etiologia , Transdução de Sinais/imunologia , Administração Cutânea , Administração Oral , Biópsia , Terapia Combinada/métodos , Comorbidade , Citocinas/antagonistas & inibidores , Citocinas/metabolismo , Fármacos Dermatológicos/farmacologia , Humanos , Terapia de Alvo Molecular/métodos , Mutação , Fototerapia/métodos , Psoríase/epidemiologia , Psoríase/psicologia , Psoríase/terapia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Transdução de Sinais/efeitos dos fármacos , Pele/imunologia , Pele/microbiologia , Pele/patologia , Fumar/efeitos adversos , Fumar/epidemiologia , Staphylococcus/imunologia , Resultado do Tratamento
12.
Nat Commun ; 10(1): 5714, 2019 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-31844063

RESUMO

The airway microbiome has an important role in asthma pathophysiology. However, little is known on the relationships between the airway microbiome of asthmatic children, loss of asthma control, and severe exacerbations. Here we report that the microbiota's dynamic patterns and compositions are related to asthma exacerbations. We collected nasal blow samples (n = 319) longitudinally during a clinical trial at 2 time-points within one year: randomization when asthma is under control, and at time of early loss of asthma control (yellow zone (YZ)). We report that participants whose microbiota was dominated by the commensal Corynebacterium + Dolosigranulum cluster at RD experience the lowest rates of YZs (p = 0.005) and have longer time to develop at least 2 episodes of YZ (p = 0.03). The airway microbiota have changed from randomization to YZ. A switch from the Corynebacterium + Dolosigranulum cluster at randomization to the Moraxella- cluster at YZ poses the highest risk of severe asthma exacerbation (p = 0.04). Corynebacterium's relative abundance at YZ is inversely associated with severe exacerbation (p = 0.002).


Assuntos
Asma/diagnóstico , Fluticasona/uso terapêutico , Interações entre Hospedeiro e Microrganismos/imunologia , Microbiota/imunologia , Simbiose/imunologia , Administração por Inalação , Asma/tratamento farmacológico , Asma/imunologia , Asma/microbiologia , Carnobacteriaceae/imunologia , Carnobacteriaceae/isolamento & purificação , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Moraxella/imunologia , Moraxella/isolamento & purificação , Mucosa Nasal/imunologia , Mucosa Nasal/microbiologia , Estudos Prospectivos , Índice de Gravidade de Doença , Staphylococcus/imunologia , Staphylococcus/isolamento & purificação , Streptococcus/imunologia , Streptococcus/isolamento & purificação , Exacerbação dos Sintomas , Resultado do Tratamento
13.
Future Microbiol ; 14: 1159-1170, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31512519

RESUMO

Staphylococci are common inhabitants at several human body sites and are also implicated in infections either as primary or opportunistic pathogens. These bacteria can thus both contribute to the host defense being a part of the commensalistic microbiota or synergize with the other microbes during the infection process. Among fungi, staphylococci interact synergistically with Candida spp. and Aspergillus fumigatus, and antagonistically with Cryptococcus neoformans and Trichosporon asahii. These interactions are highly dynamic and are orchestrated by a multitude of microbial and host factors. During such cross-talks, staphylococci can modulate the virulence, immune response or drug resistance of the coexisting microbe(s), thereby influencing the infection course, disease severity, treatment strategy and the clinical outcome.


Assuntos
Fungos/crescimento & desenvolvimento , Fungos/patogenicidade , Interações Microbianas , Staphylococcus/crescimento & desenvolvimento , Staphylococcus/patogenicidade , Fungos/imunologia , Humanos , Staphylococcus/imunologia
14.
PLoS One ; 14(9): e0217668, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31490930

RESUMO

Antibodies are essential to functional immunity, yet the epitopes targeted by antibody repertoires remain largely uncharacterized. To aid in characterization, we developed a generalizable strategy to predict antibody-binding epitopes within individual proteins and entire proteomes. Specifically, we selected antibody-binding peptides for 273 distinct sera out of a random library and identified the peptides using next-generation sequencing. To predict antibody-binding epitopes and the antigens from which these epitopes were derived, we tiled the sequences of candidate antigens into short overlapping subsequences of length k (k-mers). We used the enrichment over background of these k-mers in the antibody-binding peptide dataset to predict antibody-binding epitopes. As a positive control, we used this approach, termed K-mer Tiling of Protein Epitopes (K-TOPE), to predict epitopes targeted by monoclonal and polyclonal antibodies of well-characterized specificity, accurately recovering their known epitopes. K-TOPE characterized a commonly targeted antigen from Rhinovirus A, predicting four epitopes recognized by antibodies present in 87% of sera (n = 250). An analysis of 2,908 proteins from 400 viral taxa that infect humans predicted seven enterovirus epitopes and five Epstein-Barr virus epitopes recognized by >30% of specimens. Analysis of Staphylococcus and Streptococcus proteomes similarly predicted 22 epitopes recognized by >30% of specimens. Twelve of these common viral and bacterial epitopes agreed with previously mapped epitopes with p-values < 0.05. Additionally, we predicted 30 HSV2-specific epitopes that were 100% specific against HSV1 in novel and previously reported antigens. Experimentally validating these candidate epitopes could help identify diagnostic biomarkers, vaccine components, and therapeutic targets. The K-TOPE approach thus provides a powerful new tool to elucidate the organisms, antigens, and epitopes targeted by human antibody repertoires.


Assuntos
Epitopos/imunologia , Proteoma/imunologia , Proteômica/métodos , Análise de Sequência de Proteína/métodos , Adolescente , Adulto , Idoso , Algoritmos , Anticorpos/química , Anticorpos/imunologia , Antígenos de Bactérias/química , Antígenos de Bactérias/imunologia , Antígenos Virais/química , Antígenos Virais/imunologia , Criança , Enterovirus/imunologia , Epitopos/química , Humanos , Pessoa de Meia-Idade , Proteoma/química , Staphylococcus/imunologia , Streptococcus/imunologia
15.
Clin Rheumatol ; 38(11): 3297-3305, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31338700

RESUMO

OBJECTIVE: Antineutrophil cytoplasmic antibodies (ANCAs) are considered a risk factor for granulomatosis with polyangiitis (GPA) exacerbation, especially when staphylococcal superantigens (SAgs) are present in nasal swabs. Their role in monitoring disease activity remains controversial. This study determined the relationship of ANCAs with disease activity and presence of SAgs in GPA patients. METHODS: Among a total of 115 GPA patients hospitalized in the period 2009-2016, we investigated the presence of SAgs and ANCA concentration. Blood samples and nasal swabs were taken at each visit (referred further to as episodes). Disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS). RESULTS: We analyzed 362 episodes. ANCAs were detected in 215 (59.4%), while SAgs were detected in 126 (34.8%) episodes. We found a significant correlation between the presence of ANCAs and disease activity (p = 0.0032), as well as between their level and GPA severity (r = 0.25363, p = 0.000001). We also determined that an ANCA values ≥ 138 Ru/ml were an indicator of active disease with high specificity and low sensitivity (84.4% and 37.3%, respectively). The relationship between ANCA presence and the presence of SAgs was not confirmed; however, when SAgs were analyzed based on the different types, ANCA levels were found to be significantly higher in the group with SAg type B (p = 0.031). CONCLUSIONS: There was no detectable evidence for the association between ANCA level and the presence of SAgs. Although monitoring ANCA levels as a marker of disease activity may be clinically relevant, GPA management cannot proceed on the basis of ANCA levels alone. Key Points • ANCA concentration usually correlates with GPA activity, although in half of patients, ANCAs persist despite effective treatment and clinical remission. • ANCA values of 138 Ru/ml seem to be an indicator of active disease with high specificity, but low sensitivity. • Although there is a relevance for ANCA monitoring as a marker of disease activity, GPA management cannot be based on ANCA levels alone. • The suspected clinical correlation between ANCA formation and SAg presence in nasal swabs is not obvious and requires further investigations.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos/metabolismo , Granulomatose com Poliangiite/imunologia , Staphylococcus/imunologia , Superantígenos/metabolismo , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
PLoS One ; 14(7): e0219817, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31335868

RESUMO

The success of staphylococci as pathogens has been attributed, in part, to their ability to evade their hosts' immune systems. Although the proteins involved in evasion have been extensively studied in staphylococci affecting humans little characterization has been done with Staphylococcus pseudintermedius, an important cause of pyoderma in dogs. Staphylococcus aureus binder of immunoglobulin (Sbi) interferes with innate immune recognition by interacting with multiple host proteins. In this study, a S. pseudintermedius gene that shares 38% similarity to S. aureus Sbi was cloned from S. pseudintermedius strains representative of major clonal lineages bearing two paralogs of the protein. Binding of immunoglobulins and Fab and Fc fragments as well as interaction with complement was measured. S. pseudintermedius Sbi protein bound IgG from multiple species and canine complement C3, neutralized complement activity and bound to canine IgM and B cells. Evidence from this work suggests Sbi may play an important role in S. pseudintermedius immune evasion.


Assuntos
Proteínas de Bactérias/genética , Proteínas de Transporte/genética , Proteínas do Sistema Complemento/imunologia , Fragmentos Fab das Imunoglobulinas/imunologia , Fragmentos Fc das Imunoglobulinas/imunologia , Imunoglobulina M/imunologia , Staphylococcus/imunologia , Animais , Proteínas de Bactérias/imunologia , Proteínas de Transporte/imunologia , Cães , Homologia de Sequência de Aminoácidos , Staphylococcus/genética
17.
Front Immunol ; 10: 1269, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31231389

RESUMO

Asthma is a common chronic inflammatory disease, which is characterized by airway hyperresponsiveness (AHR), high serum levels of immunoglobulin (Ig)E, and recruitment of various inflammatory cells such as eosinophils and lymphocytes. Korean traditional fermented foods have been reported to exert beneficial effects against allergic diseases such as asthma and atopic dermatitis. In this study, we investigated whether Staphylococcus succinus strain 14BME20 (14BME20) isolated from doenjang, a traditional high-salt-fermented soybean food of Korea, exerts suppressive effects on allergic airway inflammation in a murine model. Mice were orally administered with 14BME20, then sensitized and challenged with ovalbumin as an allergen. Administration of the 14BME20 significantly suppressed AHR and influx of inflammatory cells into the lungs and reduced serum IgE levels. Moreover, the proportion of T helper type 2 (Th2) cells and the production of Th2 cytokines were decreased in 14BME20-treated mice, whereas dendritic cells (DCs) with tolerogenic characteristics were increased. In contrast, oral administration of 14BME20 increased the proportion of CD4+CD25+Foxp3+ regulatory T (Treg) cells and the level of interleukin (IL)-10 in 14BME20-treated mice. Furthermore, 14BME20 induced maturation of tolerogenic DCs, and 14BME20-treated DCs increased Treg cell population in a co-culture system of DCs and CD4+ T cells. The addition of a neutralizing anti-IL-10 mAb to the culture of cells that had been treated with 14BME20 decreased the enhanced Treg cell population, thereby indicating that 14BME20-treated DCs increase Treg cell population via DC-derived IL-10. These results demonstrate that oral administration of 14BME20 suppresses airway inflammation by enhancing Treg responses and suggest that the 14BME20 isolated from doenjang may be a therapeutic agent for allergic asthma.


Assuntos
Hiper-Reatividade Brônquica/imunologia , Hiper-Reatividade Brônquica/metabolismo , Microbiologia de Alimentos , Interleucina-10/metabolismo , Staphylococcus/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Animais , Asma/imunologia , Asma/metabolismo , Asma/patologia , Asma/prevenção & controle , Hiper-Reatividade Brônquica/patologia , Hiper-Reatividade Brônquica/prevenção & controle , Citocinas/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Modelos Animais de Doenças , Suscetibilidade a Doenças , Feminino , Tolerância Imunológica , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Mediadores da Inflamação/metabolismo , Camundongos
18.
Eur Rev Med Pharmacol Sci ; 23(1 Suppl): 48-54, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30920632

RESUMO

OBJECTIVE: The aim of our study was to search for evidence of a "staphylococcus superantigen" in chronic rhinosinusitis with nasal polyps. PATIENTS AND METHODS: Sixty-nine patients with chronic rhinosinusitis with nasal polyps and 45 healthy controls were included in the study. All patients in the study and control groups underwent bacteriological and immunological examination on nasal smear samples. Total IgE and the following cytokines were tested in all patients: tumor necrosis factor (TNF), interleukin-1 (IL1), interleukin-6 (IL6), interleukin-8 (IL8). RESULTS: The concentration of bacteria in the nasal cavity was much higher in patients in the study group compared to those in the control group, mainly due to staphylococci. In species identification of staphylococci, bacteria most represented were S. aureus and S. epidermidis. The greater the concentration of S. aureus, the lower the level of IgE. Proinflammatory cytokines were uniformly increased in patients with nasal polyps. The level of IgE was maximal in patients with chronic rhinosinusitis with nasal polyps with a poor growth of culture and minimal in patients with abundant growth, suggesting that in the latter the effect of eosinophilic inflammation on the disease was reduced, and conversely, the activity of eosinophilic inflammation was maximal with a poor seeding of the nasal cavity. CONCLUSIONS: Although this study has some limits, our findings do not support the theory of a staphylococcus superantigen in which the IgE level and eosinophilic inflammation should increase with increasing activity of Staphylococcus aureus. Further research supported by a larger sample of patients is required to better delineate the role of a staphylococcus superantigen in the pathogenesis of patients with chronic rhinosinusitis with nasal polyps.


Assuntos
Pólipos Nasais/imunologia , Infecções Estafilocócicas/imunologia , Staphylococcus/imunologia , Superantígenos/metabolismo , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Citocinas/metabolismo , Feminino , Humanos , Imunoglobulina E/metabolismo , Masculino , Pessoa de Meia-Idade , Cavidade Nasal/metabolismo , Cavidade Nasal/microbiologia , Pólipos Nasais/complicações , Pólipos Nasais/microbiologia , Rinite/complicações , Rinite/imunologia , Rinite/microbiologia , Sinusite/complicações , Sinusite/imunologia , Sinusite/microbiologia , Infecções Estafilocócicas/microbiologia , Adulto Jovem
19.
Microbiome ; 7(1): 25, 2019 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-30764863

RESUMO

BACKGROUND: Increased autoreactive antibodies have been reported in HIV disease; however, the mechanism accounting for autoantibody induction in HIV remains unknown. RESULTS: Herein, we show that seasonal influenza vaccination induces autoantibody production (e.g., IgG anti-nuclear antibody (ANA) and anti-double-stranded DNA antibody (anti-dsDNA)) in some viral-suppressed antiretroviral therapy (ART)-treated HIV+ subjects, but not in healthy controls. These autoantibodies were not derived from antigen-specific B cells but from activated "bystander" B cells analyzed by single-cell assay and by study of purified polyclonal ANAs from plasma. To explore the mechanism of autoantibody generation in HIV+ subjects, plasma level of microbial products, gene expression profile of B cells, and B cell receptor (BCR) repertoires were analyzed. We found that autoantibody production was associated with increased plasma level of microbial translocation; the patients with high autoantibodies had skewed B cell repertoires and upregulation of genes related to innate immune activation in response to microbial translocation. By analyzing circulating microbial 16S rDNA in plasma, the relative abundance of Staphylococcus was found to be associated with autoantibody production in HIV+ subjects. Finally, we found that injection of heat-killed Staphylococcus aureus promoted germinal center B cell responses and autoantibody production in mice, consistent with the notion that autoantibody production in HIV+ patients is triggered by microbial products. CONCLUSIONS: Our results showed that translocation of Staphylococcus can promote B cell activation through enhancing germinal center response and induces autoantibody production. It uncovers a potential mechanism linking microbial translocation and autoimmunity in HIV+ disease and provides a strong rationale for targeting Staphylococcus to prevent autoantibody production.


Assuntos
Autoanticorpos/metabolismo , Translocação Bacteriana , Infecções por HIV/imunologia , Vacinas contra Influenza/imunologia , Staphylococcus/fisiologia , Animais , Autoanticorpos/sangue , DNA Bacteriano/sangue , DNA Ribossômico/sangue , Modelos Animais de Doenças , Centro Germinativo/imunologia , Células Hep G2 , Humanos , Imunidade Inata , Influenza Humana/prevenção & controle , Ativação Linfocitária , Masculino , Camundongos , Análise de Célula Única , Staphylococcus/genética , Staphylococcus/imunologia , Regulação para Cima
20.
Biochem Biophys Res Commun ; 511(2): 350-355, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30795864

RESUMO

Staphylococcal superantigen-like (SSL) protein is a family of exotoxins that consists of 14 SSLs, and the roles of several SSLs in immune evasion of the cocci have been revealed. However little is known whether they act as immune activators and are involved in inflammatory disorders such as atopic dermatitis. In this study we examined whether SSLs activate mast cells, the key player of local inflammation. SSL12 evoked the release of a granule enzyme ß-hexosaminidase from bone marrow derived mast cells (BMMCs) in the absence of IgE. The release of the granule enzyme caused by SSL12 was not accompanied with the leakage of a cytosolic enzyme lactate dehydrogenase (LDH), unlike staphylococcal δ-toxin that was reported to induce both the release of ß-hexosaminidase and the leakage of LDH from the cells, suggesting that SSL12 evokes the degranulation of mast cells without cell membrane damage. Furthermore SSL12 induced IL-6 and IL-13 in both mRNA and protein levels indicating that SSL12 induces de novo synthesis of the cytokines. Evans blue extravasation was elevated by the intradermal injection of SSL12, suggesting that SSL12 is also able to evoke local inflammation in vivo. These findings indicate the novel mast cell activating activity of SSLs, and SSL12 is likely an important factor in both initiation phase and effector phase of allergic and immune responses.


Assuntos
Mastócitos/microbiologia , Staphylococcus/imunologia , Superantígenos/imunologia , Animais , Degranulação Celular , Células Cultivadas , Citocinas/imunologia , Interações Hospedeiro-Patógeno , Mastócitos/imunologia , Mastócitos/fisiologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia
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