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[PMID]:29458538
[Au] Autor:Ma J; Yu L; Song B; Yu Y; Zhang S; Wei Y; Wu Z; Yao D; Yu W; Zhu Z; Cui Y
[Ad] Endereço:1​College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, PR China.
[Ti] Título:The double adjuvants LTB and CpG significantly enhanced the immuno-protective effects of recombinant GIT derived from Staphylococcus aureus and Streptococcus in mice.
[So] Source:J Med Microbiol;67(3):432-440, 2018 Mar.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PURPOSE: In this study, we prepared GapC1-150-IsdB126-361-TRAP (GIT) proteins plus heat-labile enterotoxin B (LTB) as an intra-molecular adjuvant, together with CpG to further enhance its immunogenicity. METHODOLOGY: Initially, the target genes were acquired and inserted into pET-32a (+) vectors to express LTB-GIT protein. LTB-GIT expression was confirmed by Western blotting and its immunocompetence was estimated through ELISA. Further, we immunized BALB/c mice with the LTB-GIT plus CpG adjuvant. After the second immunization, the antigen-specific CD4 cell responses for IFN-γ, IL-2, IL-4 and IL-10 were monitored by intracellular cytokine staining (ICS) assay. After the third immunization, the level of IgG antibodies in the serum from immunized groups was assessed by ELISA, and the protective immune response was appraised by Staphylococcus aureus and Streptococcus dysgalactiae challenge. RESULTS: The ELISA results showed that the OD450nm value of the LTB-GIT group was significantly higher than that of the BSA group. The group immunized with LTB-GIT plus CpG exhibited significantly stronger CD4 T cell responses for IFN-γ, IL-2, IL-4 and IL-10 compared to the group immunized with LTB-GIT, GIT alone orLTB-GIT plus CpG. In addition, the group immunized with LTB-GIT plus CpG generated the highest level of IgG antibodies against GIT among all of the groups, and our results also showed that LTB-GIT plus CpG markedly improved the survival percentage of mice compared to other groups. CONCLUSION: We confirmed that the novel double adjuvants, LTB and CpG, are able to significantly improve GIT-induced immune responses. This formula could be a promising strategy for enhancing the immune efficacy of multi-subunit vaccines against Staphylococcus aureus and streptococcal infection.
[Mh] Termos MeSH primário: Adjuvantes Imunológicos
Toxinas Bacterianas/imunologia
Vacinas Bacterianas/imunologia
Enterotoxinas/imunologia
Oligodesoxirribonucleotídeos/imunologia
Staphylococcus aureus/imunologia
Streptococcus/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Antibacterianos/sangue
Antígenos de Bactérias/imunologia
Proteínas de Bactérias/imunologia
Toxinas Bacterianas/administração & dosagem
Toxinas Bacterianas/genética
Linfócitos T CD4-Positivos
Enterotoxinas/administração & dosagem
Enterotoxinas/genética
Feminino
Interferon gama/imunologia
Interleucina-10/imunologia
Interleucina-2/imunologia
Interleucina-4/imunologia
Camundongos
Camundongos Endogâmicos BALB C
Oligodesoxirribonucleotídeos/genética
Proteínas Recombinantes/genética
Proteínas Recombinantes/imunologia
Infecções Estafilocócicas/imunologia
Staphylococcus aureus/química
Infecções Estreptocócicas/imunologia
Streptococcus/química
Vacinação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adjuvants, Immunologic); 0 (Antibodies, Bacterial); 0 (Antigens, Bacterial); 0 (Bacterial Proteins); 0 (Bacterial Toxins); 0 (Bacterial Vaccines); 0 (CPG-oligonucleotide); 0 (Enterotoxins); 0 (IL10 protein, mouse); 0 (Interleukin-2); 0 (Oligodeoxyribonucleotides); 0 (Recombinant Proteins); 130068-27-8 (Interleukin-10); 207137-56-2 (Interleukin-4); 82115-62-6 (Interferon-gamma)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180221
[St] Status:MEDLINE
[do] DOI:10.1099/jmm.0.000666


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[PMID]:28466091
[Au] Autor:Li S; Sha Z; Wang X; Bu Z; Wang L; Guan X; Lang X; Wang X
[Ad] Endereço:Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, Jilin, China.
[Ti] Título:Yeast Surface Display of Escherichia coli Enterotoxin and Its Effects of Intestinal Microflora and Mucosal Immunity.
[So] Source:Curr Microbiol;74(7):854-862, 2017 Jul.
[Is] ISSN:1432-0991
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Enterotoxigenic Escherichia coli (ETEC) is a significant cause of infectious diarrhea in animals. In this study, yeast surface display technology was employed to investigate the effects of ETEC enterotoxin fusion protein on the intestinal flora and mucosal immunity of rats. ETEC estA, estB, and eltAB (heat-labile and heat-stable toxins) were expressed on the surface of yeast. Rats were divided into normal saline, yeast and display yeast groups. Fecal and jejunal content samples were collected on the 7th, 14th, and 21st days. Rats were then fed ETEC for 3 days before again collecting these samples. Levels of SIgA, IL-2, IL-4, IFN-γ, and microbial population density and diversity were documented by ELISA, T-RFLP and real-time PCR. The results demonstrated that estA, estB, and eltAB fusion proteins were expressed on the surface of yeast. Following ETEC challenge, levels of SIgA, IL-2, IL-4, IFN-γ, and, the numbers and variety of intestinal microbes were significantly increased in rats receiving display yeast and yeast. These factors were significantly decreased in rats given normal saline and yeast. Our results indicate that display yeast and yeast can increase the number and diversity of intestinal microbes in rats and improve intestinal immune function. After ETEC challenge, the display yeast can better maintain the balance of intestinal bacteria and mucosal immunity.
[Mh] Termos MeSH primário: Toxinas Bacterianas/genética
Enterotoxinas/genética
Infecções por Escherichia coli/microbiologia
Escherichia coli/genética
Microbioma Gastrointestinal
Expressão Gênica
Imunidade nas Mucosas
Intestinos/microbiologia
Saccharomyces cerevisiae/genética
[Mh] Termos MeSH secundário: Animais
Toxinas Bacterianas/imunologia
Enterotoxinas/metabolismo
Escherichia coli/metabolismo
Infecções por Escherichia coli/imunologia
Seres Humanos
Intestinos/imunologia
Ratos
Ratos Sprague-Dawley
Saccharomyces cerevisiae/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Toxins); 0 (Enterotoxins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1007/s00284-017-1259-1


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[PMID]:28468970
[Au] Autor:Chowdhary VR; Krogman A; Tilahun AY; Alexander MP; David CS; Rajagopalan G
[Ad] Endereço:Division of Rheumatology, Department of Medicine, Mayo Clinic, Rochester, MN 55905.
[Ti] Título:Concomitant Disruption of and Genes Facilitates the Development of Double Negative αß TCR Peripheral T Cells That Respond Robustly to Staphylococcal Superantigen.
[So] Source:J Immunol;198(11):4413-4424, 2017 06 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mature peripheral double negative T (DNT) cells expressing αß TCR but lacking CD4/CD8 coreceptors play protective as well as pathogenic roles. To better understand their development and functioning in vivo, we concomitantly inactivated and genes in mice with intact MHC class I and class II molecules with the hypothesis that this would enable the development of DNT cells. We also envisaged that these DNT cells could be activated by bacterial superantigens in vivo as activation of T cells by superantigens does not require CD4 and CD8 coreceptors. Because HLA class II molecules present superantigens more efficiently than murine MHC class II molecules, CD4 CD8 double knockout (DKO) mice transgenically expressing HLA-DR3 or HLA-DQ8 molecules were generated. Although thymic cellularity was comparable between wild type (WT) and DKO mice, CD3 αß TCR thymocytes were significantly reduced in DKO mice, implying defects in thymic-positive selection. Splenic CD3 αß TCR cells and Foxp3 T regulatory cells were present in DKO mice but significantly reduced. However, the in vivo inflammatory responses and immunopathology elicited by acute challenge with the staphylococcal superantigen enterotoxin B were comparable between WT and DKO mice. Choric exposure to staphylococcal enterotoxin B precipitated a lupus-like inflammatory disease with characteristic lympho-monocytic infiltration in lungs, livers, and kidneys, along with production of anti-nuclear Abs in DKO mice as in WT mice. Overall, our results suggest that DNT cells can develop efficiently in vivo and chronic exposure to bacterial superantigens may precipitate a lupus-like autoimmune disease through activation of DNT cells.
[Mh] Termos MeSH primário: Antígenos CD4/genética
Antígenos CD4/imunologia
Antígenos CD8/genética
Antígenos CD8/imunologia
Enterotoxinas/imunologia
Superantígenos/imunologia
Subpopulações de Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Animais
Antígenos HLA-DQ/genética
Antígenos HLA-DQ/imunologia
Antígeno HLA-DR3/genética
Antígeno HLA-DR3/imunologia
Antígenos de Histocompatibilidade Classe II/imunologia
Camundongos
Camundongos Knockout
Camundongos Transgênicos
Receptores de Antígenos de Linfócitos T alfa-beta/genética
Receptores de Antígenos de Linfócitos T alfa-beta/imunologia
Baço/citologia
Baço/imunologia
Timo/citologia
Timo/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (CD4 Antigens); 0 (CD8 Antigens); 0 (Enterotoxins); 0 (HLA-DQ Antigens); 0 (HLA-DQ8 antigen); 0 (HLA-DR3 Antigen); 0 (Histocompatibility Antigens Class II); 0 (Receptors, Antigen, T-Cell, alpha-beta); 0 (Superantigens); 39424-53-8 (enterotoxin B, staphylococcal)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180127
[Lr] Data última revisão:
180127
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1601991


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[PMID]:29211241
[Au] Autor:Cunha CEPD; Moreira C; Rocha ADSR; Finger PF; Magalhães CG; Ferreira MRA; Dellagostin OA; Moreira ÂN; Conceição FR
[Ad] Endereço:Universidade Federal de Pelotas, Centro de Desenvolvimento Tecnológico, Biotecnologia, Pelotas, RS, Brasil.
[Ti] Título:Parenteral adjuvant potential of recombinant B subunit of Escherichia coli heat-labile enterotoxin.
[So] Source:Mem Inst Oswaldo Cruz;112(12):812-816, 2017 Dec.
[Is] ISSN:1678-8060
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The B subunit of Escherichia coli heat-labile enterotoxin (LTB) is a potent mucosal immune adjuvant. However, there is little information about LTB's potential as a parenteral adjuvant. OBJECTIVES: We aimed at evaluating and better understanding rLTB's potential as a parenteral adjuvant using the fused R1 repeat of Mycoplasma hyopneumoniae P97 adhesin as an antigen to characterise the humoral immune response induced by this construct and comparing it to that generated when aluminium hydroxide is used as adjuvant instead. METHODS: BALB/c mice were immunised intraperitoneally with either rLTBR1 or recombinant R1 adsorbed onto aluminium hydroxide. The levels of systemic anti-rR1 antibodies (total Ig, IgG1, IgG2a, and IgA) were assessed by enzyme-linked immunosorbent assay (ELISA). The ratio of IgG1 and IgG2a was used to characterise a Th1, Th2, or mixed Th1/Th2 immune response. FINDINGS: Western blot confirmed rR1, either alone or fused to LTB, remained antigenic; anti-cholera toxin ELISA confirmed that LTB retained its activity when expressed in a heterologous system. Mice immunised with the rLTBR1 fusion protein produced approximately twice as much anti-rR1 immunoglobulins as mice vaccinated with rR1 adsorbed onto aluminium hydroxide. Animals vaccinated with either rLTBR1 or rR1 adsorbed onto aluminium hydroxide presented a mixed Th1/Th2 immune response. We speculate this might be a result of rR1 immune modulation rather than adjuvant modulation. Mice immunised with rLTBR1 produced approximately 1.5-fold more serum IgA than animals immunised with rR1 and aluminium hydroxide. MAIN CONCLUSIONS: The results suggest that rLTB is a more powerful parenteral adjuvant than aluminium hydroxide when administered intraperitoneally as it induced higher antibody titres. Therefore, we recommend that rLTB be considered an alternative adjuvant, even if different administration routes are employed.
[Mh] Termos MeSH primário: Adesinas Bacterianas/imunologia
Adjuvantes Imunológicos/administração & dosagem
Toxinas Bacterianas/administração & dosagem
Enterotoxinas/administração & dosagem
Proteínas de Escherichia coli/administração & dosagem
Mycoplasma hyopneumoniae/imunologia
Pneumonia Suína Micoplasmática/prevenção & controle
[Mh] Termos MeSH secundário: Hidróxido de Alumínio
Animais
Toxinas Bacterianas/imunologia
Enterotoxinas/imunologia
Ensaio de Imunoadsorção Enzimática
Proteínas de Escherichia coli/imunologia
Feminino
Camundongos
Camundongos Endogâmicos BALB C
Pneumonia Suína Micoplasmática/imunologia
Suínos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adhesins, Bacterial); 0 (Adjuvants, Immunologic); 0 (Bacterial Toxins); 0 (Enterotoxins); 0 (Escherichia coli Proteins); 0 (P97 protein, Mycoplasma); 0 (heat-labile enterotoxin, E coli); 5QB0T2IUN0 (Aluminum Hydroxide)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171227
[Lr] Data última revisão:
171227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171207
[St] Status:MEDLINE


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[PMID]:28947540
[Au] Autor:Matta P; Sherrod SD; Marasco CC; Moore DJ; McLean JA; Weitkamp JH
[Ad] Endereço:Department of Pediatrics, Vanderbilt University Medical Center, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, TN 37232.
[Ti] Título:In Utero Exposure to Histological Chorioamnionitis Primes the Exometabolomic Profiles of Preterm CD4 T Lymphocytes.
[So] Source:J Immunol;199(9):3074-3085, 2017 Nov 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Histological chorioamnionitis (HCA) is an intrauterine inflammatory condition that increases the risk for preterm birth, death, and disability because of persistent systemic and localized inflammation. The immunological mechanisms sustaining this response in the preterm newborn remain unclear. We sought to determine the consequences of HCA exposure on the fetal CD4 T lymphocyte exometabolome. We cultured naive CD4 T lymphocytes from HCA-positive and -negative preterm infants matched for gestational age, sex, race, prenatal steroid exposure, and delivery mode. We collected conditioned media samples before and after a 6-h in vitro activation of naive CD4 T lymphocytes with soluble staphylococcal enterotoxin B and anti-CD28. We analyzed samples by ultraperformance liquid chromatography ion mobility-mass spectrometry. We determined the impact of HCA on the CD4 T lymphocyte exometabolome and identified potential biomarker metabolites by multivariate statistical analyses. We discovered that: 1) CD4 T lymphocytes exposed to HCA exhibit divergent exometabolomic profiles in both naive and activated states; 2) ∼30% of detected metabolites differentially expressed in response to activation were unique to HCA-positive CD4 T lymphocytes; 3) metabolic pathways associated with glutathione detoxification and tryptophan degradation were altered in HCA-positive CD4 T lymphocytes; and 4) flow cytometry and cytokine analyses suggested a bias toward a T 1-biased immune response in HCA-positive samples. HCA exposure primes the neonatal adaptive immune processes by inducing changes to the exometabolomic profile of fetal CD4 T lymphocytes. These exometabolomic changes may link HCA exposure to T 1 polarization of the neonatal adaptive immune response.
[Mh] Termos MeSH primário: Corioamnionite/imunologia
Corioamnionite/metabolismo
Células Th1/imunologia
Células Th1/metabolismo
[Mh] Termos MeSH secundário: Biomarcadores/metabolismo
Corioamnionite/patologia
Enterotoxinas/farmacologia
Feminino
Seres Humanos
Recém-Nascido
Recém-Nascido Prematuro
Masculino
Gravidez
Células Th1/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Enterotoxins); 39424-53-8 (enterotoxin B, staphylococcal)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170927
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1601880


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[PMID]:28922025
[Au] Autor:Ulusoy BH; Çakmak Sancar B; Öztürk M
[Ad] Endereço:1 Near East University Faculty of Veterinary Medicine Food Hygiene and Technology Department, Nicosia 99138, Turkish Republic of North Cyprus (ORCID: http://orcid.org/0000-0001-9278-2537 ); and.
[Ti] Título:Prevalence of Staphylococcal Enterotoxins in Ready-to-Eat Foods Sold in Istanbul.
[So] Source:J Food Prot;80(10):1734-1736, 2017 Oct.
[Is] ISSN:1944-9097
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The aim of this study was to investigate the prevalence of staphylococcal enterotoxins (SEs) in ready-to-eat (RTE) foods sold in Istanbul, Turkey. A total of 5,241 samples were randomly collected from various caterers, hotels, and restaurants from 2014 to 2016. The samples were classified into four groups: (i) various cooked RTE meat and vegetable meals, (ii) various RTE salads, charcuterie, and cold appetizers, (iii) various cooked RTE bakery products (pasta, pastries, pizza, pita, ravioli, etc.), and (iv) any cooked RTE sweets and desserts (pudding, custard, cream, ashura, etc.). The samples were examined for the presence of SEs by 3M Tecra Staph Enterotoxin Visual Immunoassay method, which is a manual enzyme-linked immunosorbent assay method. Among all samples, only 1 (0.019%) RTE meal (vegetable meal with meat) was found to be contaminated with SEs, a good result in terms of staphylococcal food poisoning risk and public health.
[Mh] Termos MeSH primário: Enterotoxinas/isolamento & purificação
Fast Foods/análise
Contaminação de Alimentos/análise
[Mh] Termos MeSH secundário: Microbiologia de Alimentos
Seres Humanos
Prevalência
Intoxicação Alimentar Estafilocócica/prevenção & controle
Turquia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enterotoxins)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170919
[St] Status:MEDLINE
[do] DOI:10.4315/0362-028X.JFP-16-532


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[PMID]:28902923
[Au] Autor:Salazar CL; Reyes C; Atehortua S; Sierra P; Correa MM; Paredes-Sabja D; Best E; Fawley WN; Wilcox M; González Á
[Ad] Endereço:Research Group in Anaerobic Bacteria (GIBA), School of Microbiology, Universidad de Antioquia, Medellín, Colombia.
[Ti] Título:Molecular, microbiological and clinical characterization of Clostridium difficile isolates from tertiary care hospitals in Colombia.
[So] Source:PLoS One;12(9):e0184689, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In Colombia, the epidemiology and circulating genotypes of Clostridium difficile have not yet been described. Therefore, we molecularly characterized clinical isolates of C.difficile from patients with suspicion of C.difficile infection (CDI) in three tertiary care hospitals. C.difficile was isolated from stool samples by culture, the presence of A/B toxins were detected by enzyme immunoassay, cytotoxicity was tested by cell culture and the antimicrobial susceptibility determined. After DNA extraction, tcdA, tcdB and binary toxin (CDTa/CDTb) genes were detected by PCR, and PCR-ribotyping performed. From a total of 913 stool samples collected during 2013-2014, 775 were included in the study. The frequency of A/B toxins-positive samples was 9.7% (75/775). A total of 143 isolates of C.difficile were recovered from culture, 110 (76.9%) produced cytotoxic effect in cell culture, 100 (69.9%) were tcdA+/tcdB+, 11 (7.7%) tcdA-/tcdB+, 32 (22.4%) tcdA-/tcdB- and 25 (17.5%) CDTa+/CDTb+. From 37 ribotypes identified, ribotypes 591 (20%), 106 (9%) and 002 (7.9%) were the most prevalent; only one isolate corresponded to ribotype 027, four to ribotype 078 and four were new ribotypes (794,795, 804,805). All isolates were susceptible to vancomycin and metronidazole, while 85% and 7.7% were resistant to clindamycin and moxifloxacin, respectively. By multivariate analysis, significant risk factors associated to CDI were, staying in orthopedic service, exposure to third-generation cephalosporins and staying in an ICU before CDI symptoms; moreover, steroids showed to be a protector factor. These results revealed new C. difficile ribotypes and a high diversity profile circulating in Colombia different from those reported in America and European countries.
[Mh] Termos MeSH primário: Clostridium difficile/genética
[Mh] Termos MeSH secundário: Idoso
Proteínas de Bactérias/genética
Toxinas Bacterianas/genética
Clostridium difficile/isolamento & purificação
Colômbia
Estudos Transversais
Enterocolite Pseudomembranosa/microbiologia
Enterotoxinas/genética
Feminino
Seres Humanos
Masculino
Testes de Sensibilidade Microbiana
Meia-Idade
Ribotipagem
Fatores de Risco
Centros de Atenção Terciária
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Bacterial Toxins); 0 (Enterotoxins); 0 (tcdA protein, Clostridium difficile); 0 (toxB protein, Clostridium difficile)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170914
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184689


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[PMID]:28880920
[Au] Autor:Tuffs SW; James DBA; Bestebroer J; Richards AC; Goncheva MI; O'Shea M; Wee BA; Seo KS; Schlievert PM; Lengeling A; van Strijp JA; Torres VJ; Fitzgerald JR
[Ad] Endereço:The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian, Scotland, United States of America.
[Ti] Título:The Staphylococcus aureus superantigen SElX is a bifunctional toxin that inhibits neutrophil function.
[So] Source:PLoS Pathog;13(9):e1006461, 2017 Sep.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Bacterial superantigens (SAgs) cause Vß-dependent T-cell proliferation leading to immune dysregulation associated with the pathogenesis of life-threatening infections such as toxic shock syndrome, and necrotizing pneumonia. Previously, we demonstrated that staphylococcal enterotoxin-like toxin X (SElX) from Staphylococcus aureus is a classical superantigen that exhibits T-cell activation in a Vß-specific manner, and contributes to the pathogenesis of necrotizing pneumonia. Here, we discovered that SElX can also bind to neutrophils from human and other mammalian species and disrupt IgG-mediated phagocytosis. Site-directed mutagenesis of the conserved sialic acid-binding motif of SElX abolished neutrophil binding and phagocytic killing, and revealed multiple glycosylated neutrophil receptors for SElX binding. Furthermore, the neutrophil binding-deficient mutant of SElX retained its capacity for T-cell activation demonstrating that SElX exhibits mechanistically independent activities on distinct cell populations associated with acquired and innate immunity, respectively. Finally, we demonstrated that the neutrophil-binding activity rather than superantigenicity is responsible for the SElX-dependent virulence observed in a necrotizing pneumonia rabbit model of infection. Taken together, we report the first example of a SAg, that can manipulate both the innate and adaptive arms of the human immune system during S. aureus pathogenesis.
[Mh] Termos MeSH primário: Enterotoxinas/metabolismo
Exfoliatinas/farmacologia
Neutrófilos/efeitos dos fármacos
Infecções Estafilocócicas
Superantígenos/farmacologia
[Mh] Termos MeSH secundário: Animais
Exfoliatinas/metabolismo
Seres Humanos
Ativação Linfocitária/imunologia
Neutrófilos/imunologia
Coelhos
Receptores de Antígenos de Linfócitos T alfa-beta/imunologia
Staphylococcus aureus/química
Staphylococcus aureus/metabolismo
Superantígenos/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enterotoxins); 0 (Exfoliatins); 0 (Receptors, Antigen, T-Cell, alpha-beta); 0 (Superantigens)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170908
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006461


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[PMID]:28880913
[Au] Autor:Langley RJ; Ting YT; Clow F; Young PG; Radcliff FJ; Choi JM; Sequeira RP; Holtfreter S; Baker H; Fraser JD
[Ad] Endereço:School of Medical Sciences, and The Maurice Wilkins Centre for Molecular Biodiscovery, the University of Auckland, Auckland, New Zealand.
[Ti] Título:Staphylococcal enterotoxin-like X (SElX) is a unique superantigen with functional features of two major families of staphylococcal virulence factors.
[So] Source:PLoS Pathog;13(9):e1006549, 2017 Sep.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Staphylococcus aureus is an opportunistic pathogen that produces many virulence factors. Two major families of which are the staphylococcal superantigens (SAgs) and the Staphylococcal Superantigen-Like (SSL) exoproteins. The former are immunomodulatory toxins that induce a Vß-specific activation of T cells, while the latter are immune evasion molecules that interfere with a wide range of innate immune defences. The superantigenic properties of Staphylococcal enterotoxin-like X (SElX) have recently been established. We now reveal that SElX also possesses functional characteristics of the SSLs. A region of SElX displays high homology to the sialyl-lactosamine (sLacNac)-specific binding site present in a sub-family of SSLs. By analysing the interaction of SElX with sLacNac-containing glycans we show that SElX has an equivalent specificity and host cell binding range to the SSLs. Mutation of key amino acids in this conserved region affects the ability of SElX to bind to cells of myeloid origin and significantly reduces its ability to protect S. aureus from destruction in a whole blood killing (WBK) assay. Like the SSLs, SElX is up-regulated early during infection and is under the control of the S. aureus exotoxin expression (Sae) two component gene regulatory system. Additionally, the structure of SElX in complex with the sLacNac-containing tetrasaccharide sialyl Lewis X (sLeX) reveals that SElX is a unique single-domain SAg. In summary, SElX is an 'SSL-like' SAg.
[Mh] Termos MeSH primário: Enterotoxinas/metabolismo
Exotoxinas/metabolismo
Evasão da Resposta Imune/imunologia
Infecções Estafilocócicas/metabolismo
Staphylococcus aureus/metabolismo
Fatores de Virulência/metabolismo
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Seres Humanos
Camundongos
Infecções Estafilocócicas/imunologia
Superantígenos/genética
Fatores de Virulência/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enterotoxins); 0 (Exotoxins); 0 (Superantigens); 0 (Virulence Factors)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170908
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006549


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[PMID]:28807764
[Au] Autor:Fu X; Xu M; Yao S; Zhang H; Zhang C; Zhang J
[Ad] Endereço:School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 103 WenHua Road, Shenyang 110016, PR China.
[Ti] Título:Staphylococcal enterotoxin C2 mutant drives T lymphocyte activation through PI3K/mTOR and NF-ĸB signaling pathways.
[So] Source:Toxicol Appl Pharmacol;333:51-59, 2017 Oct 15.
[Is] ISSN:1096-0333
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Staphylococcal enterotoxin C2 (SEC2), a superantigen, causes rapid clonal expansion of lymphocytes and secretion of T cell growth factors, leading to a severe inflammatory response within tissues. Although previous studies have shown that ST-4, a SEC2 mutant with enhanced recognition of Vß regions of T-cell receptors (TCRVß), can activate an increased number of T cells and produce more cytokines than SEC2. However, the signaling mechanisms of SEC2/ST-4-mediated immune activation have not been addressed. In this study, we showed that the phosphatidylinositide-3-kinase (PI-3K) inhibitor LY294002, mammalian target of rapamycin (mTOR) inhibitor rapamycin, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inhibitor Bay11-7085 could suppress SEC2/ST-4-induced proliferation, CD69/CD25 expression, cell-cycle progression, and IL-2 production in BALB/c mouse splenocytes. In addition, we observed significantly upregulated expression of p70S6K, cyclin E, cyclin D3, and NF-ĸB/p65, but downregulated expression of p27kip during SEC2/ST-4-driven T cells activation. However, SEC2/ST-4-induced changes in cell cycle and PI3K/mTOR signaling were significantly relieved by either LY294002 or rapamycin, and the induction of NF-ĸB/p65 induced was significantly downregulated by Bay11-7085. Moreover, we found that IL-2 secretion was positively associated with p65 expression in a time- and dose-dependent manner. Taken together, our findings demonstrate the involvement of PI3K/mTOR and NF-κB signaling pathways in SEC2/ST-4-induced T cell activation. ST-4 intensifies PI3K/mTOR and NF-ĸB signaling transduction, ultimately leading to enhance T cell activation. These results provide a theoretical mechanism for future immunotherapy using ST-4.
[Mh] Termos MeSH primário: Enterotoxinas/genética
Ativação Linfocitária/imunologia
NF-kappa B/imunologia
Fosfatidilinositol 3-Quinases/imunologia
Linfócitos T/imunologia
Serina-Treonina Quinases TOR/imunologia
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Feminino
Interleucina-2/imunologia
Camundongos Endogâmicos BALB C
Mutação
Transdução de Sinais
Baço/citologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enterotoxins); 0 (Interleukin-2); 0 (NF-kappa B); 39424-54-9 (enterotoxin C, staphylococcal); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 2.7.1.1 (mTOR protein, mouse)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170920
[Lr] Data última revisão:
170920
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170816
[St] Status:MEDLINE



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