Live Attenuated B. pertussis BPZE1 Rescues the Immune Functions of Respiratory Syncytial Virus Infected Human Dendritic Cells by Promoting Th1/Th17 Responses
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{"title"=>"Live attenuated B. pertussis BPZE1 rescues the immune functions of respiratory Syncytial virus infected human dendritic cells by promoting Th1/Th17 responses", "type"=>"journal", "authors"=>[{"first_name"=>"Ilaria", "last_name"=>"Schiavoni", "scopus_author_id"=>"6602634088"}, {"first_name"=>"Giorgio", "last_name"=>"Fedele", "scopus_author_id"=>"7003460880"}, {"first_name"=>"Adriano", "last_name"=>"Quattrini", "scopus_author_id"=>"52164490600"}, {"first_name"=>"Manuela", "last_name"=>"Bianco", "scopus_author_id"=>"38460899000"}, {"first_name"=>"Corinna", "last_name"=>"Schnoeller", "scopus_author_id"=>"24169832100"}, {"first_name"=>"Peter J.", "last_name"=>"Openshaw", "scopus_author_id"=>"7007035069"}, {"first_name"=>"Camille", "last_name"=>"Locht", "scopus_author_id"=>"7006712654"}, {"first_name"=>"Clara M.", "last_name"=>"Ausiello", "scopus_author_id"=>"7005948235"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84903383453", "pui"=>"373399519", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "doi"=>"10.1371/journal.pone.0100166", "issn"=>"19326203", "scopus"=>"2-s2.0-84903383453", "pmid"=>"24967823"}, "id"=>"df592c70-1526-3164-acb3-290c5fb17ea2", "abstract"=>"Respiratory Syncytial virus (RSV) is the leading cause of acute lower respiratory tract viral infection in young children and a major cause of winter hospitalization. Bordetella pertussis is a common cause of bacterial lung disease, affecting a similar age group. Although vaccines are available for B. pertussis infection, disease rates have recently increased in many countries. We have therefore developed a novel live attenuated B. pertussis strain (BPZE1), which has recently undergone a successful clinical phase I trial. In mice, BPZE1 provides protection against disease caused by respiratory viral challenge. Here, we analyze the effect of BPZE1 on antiviral T cell responses induced by human monocyte-derived dendritic cells (MDDC). We found that BPZE1 influences antiviral immune responses at several levels, enhancing MDDC maturation, IL-12p70 production, and shifting T cell cytokine profile towards a Th1/Th17 pattern. These data were supported by the intracellular signaling analysis. RSV infection of MDDC caused MyD88-independent STAT1 phosphorylation, whereas BPZE1 activated MyD88-dependent signaling pathways; co-infection caused both pathways to be activated. These findings suggest that BPZE1 given during infancy might improve the course and outcome of viral lung disease in addition to providing specific protection against B. pertussis infection.", "link"=>"http://www.mendeley.com/research/live-attenuated-b-pertussis-bpze1-rescues-immune-functions-respiratory-syncytial-virus-infected-huma", "reader_count"=>23, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>4, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>6, "Student > Master"=>7, "Other"=>1, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>4, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>6, "Student > Master"=>7, "Other"=>1, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Medicine and Dentistry"=>9, "Agricultural and Biological Sciences"=>7, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Immunology and Microbiology"=>4}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>9}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>7}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Netherlands"=>1, "United States"=>1, "Japan"=>1, "United Kingdom"=>1}, "group_count"=>2}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1568800"], "description"=>"<p>MDDC were infected with RSV (MOI of 1), BPZE1 (bacteria/cell ratio of 100∶1), or both. Mock-infected cells were added as control. After 48 h, MDDC were co-cultured with allogeneic purified T cells at increasing T cells/MDDC ratios (5/1, 10/1, 20/1, 40/1) for 6 d. Results are reported as percentages of BrdU positive cells (mean ± SEM of 4 independent experiments performed with MDDC obtained from different donors).</p>", "links"=>[], "tags"=>["cell biology", "Cellular types", "Animal cells", "Immune cells", "Antigen-presenting cells", "Dendritic cells", "Signal transduction", "cell signaling", "Signaling cascades", "MAPK signaling cascades", "immunology", "Clinical immunology", "immunomodulation", "Vaccination and immunization", "vaccines", "Attenuated vaccines", "Immunity to infections", "Infectious diseases", "Viral diseases", "Respiratory syncytial virus infection", "bpze1", "rsv-induced", "allogeneic"], "article_id"=>1085723, "categories"=>["Biological Sciences"], "users"=>["Ilaria Schiavoni", "Giorgio Fedele", "Adriano Quattrini", "Manuela Bianco", "Corinna Schnoeller", "Peter J. Openshaw", "Camille Locht", "Clara M. Ausiello"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100166.g003", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Impact_of_BPZE1_on_RSV_induced_allogeneic_T_cell_proliferation_/1085723", "title"=>"Impact of BPZE1 on RSV-induced allogeneic T cell proliferation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-26 03:22:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/1568801"], "description"=>"<p>MDDC were treated with BPZE1 (bacteria/cell ratio of 100∶1), RSV (MOI of 1) or both. Mock-infected cells were added as control. After 48 h, treated MDDC were cultured with purified allogeneic CD3 T cells. On day12, supernatants were collected, and IFN-γ (Th1), IL-5 (Th2) and IL-17 (Th17) were measured by ELISA. Values are expressed as medians with interquartile range of 13 independent experiments performed with MDDC obtained from different donors and expressed as ng/ml (IFNγ) or pg/ml (IL-5 and IL-17). Statistical significant differences are indicated by * (<i>P</i>≤0.0083).</p>", "links"=>[], "tags"=>["cell biology", "Cellular types", "Animal cells", "Immune cells", "Antigen-presenting cells", "Dendritic cells", "Signal transduction", "cell signaling", "Signaling cascades", "MAPK signaling cascades", "immunology", "Clinical immunology", "immunomodulation", "Vaccination and immunization", "vaccines", "Attenuated vaccines", "Immunity to infections", "Infectious diseases", "Viral diseases", "Respiratory syncytial virus infection", "bpze1", "rsv-induced", "lymphocyte"], "article_id"=>1085724, "categories"=>["Biological Sciences"], "users"=>["Ilaria Schiavoni", "Giorgio Fedele", "Adriano Quattrini", "Manuela Bianco", "Corinna Schnoeller", "Peter J. Openshaw", "Camille Locht", "Clara M. Ausiello"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100166.g004", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Impact_of_BPZE1_on_RSV_induced_T_lymphocyte_polarization_/1085724", "title"=>"Impact of BPZE1 on RSV-induced T lymphocyte polarization.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-26 03:22:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/1568789"], "description"=>"<p>MDDC were treated with BPZE1 (bacteria/cell ratio of 100∶1), RSV (MOI of 1) or double infected with BPZE1 and RSV. Mock-infected cells were used as control. After 24 h, cytokines released in the culture media were measured by ELISA. Values are expressed as medians with interquartile range from 13 (IL-10 and IL-23) and from 15 (IL-12p70) independent experiments performed with MDDC obtained from different donors and expressed as ng/ml (IL-10) or pg/ml (IL-12p70 and IL-23). Statistical significant differences are indicated by * (<i>P</i>≤0.0083).</p>", "links"=>[], "tags"=>["cell biology", "Cellular types", "Animal cells", "Immune cells", "Antigen-presenting cells", "Dendritic cells", "Signal transduction", "cell signaling", "Signaling cascades", "MAPK signaling cascades", "immunology", "Clinical immunology", "immunomodulation", "Vaccination and immunization", "vaccines", "Attenuated vaccines", "Immunity to infections", "Infectious diseases", "Viral diseases", "Respiratory syncytial virus infection", "bpze1", "il-12p70", "il-23", "rsv-infected"], "article_id"=>1085721, "categories"=>["Biological Sciences"], "users"=>["Ilaria Schiavoni", "Giorgio Fedele", "Adriano Quattrini", "Manuela Bianco", "Corinna Schnoeller", "Peter J. Openshaw", "Camille Locht", "Clara M. Ausiello"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100166.g002", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Impact_of_BPZE1_on_IL_10_IL_12p70_and_IL_23_production_of_RSV_infected_MDDC_/1085721", "title"=>"Impact of BPZE1 on IL-10, IL-12p70 and IL-23 production of RSV-infected MDDC.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-26 03:22:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/1568780"], "description"=>"<p>MDDC were treated with BPZE1 (bacteria/cell ratio 100∶1), RSV (MOI of 1) or both. After 24 h, cells were analyzed for the indicated surface markers associated with a mature phenotype. Mock-infected cells were used as control. Fluorescence data are reported as median fluorescence intensity (MedFI) for CD80 and CD38, and as percentage of positive cells for CD83. Values are expressed as medians with interquartile range of seven independent experiments performed with MDDC obtained from different donors. Statistical significant differences are indicated by * (<i>P</i>≤0.0083).</p>", "links"=>[], "tags"=>["cell biology", "Cellular types", "Animal cells", "Immune cells", "Antigen-presenting cells", "Dendritic cells", "Signal transduction", "cell signaling", "Signaling cascades", "MAPK signaling cascades", "immunology", "Clinical immunology", "immunomodulation", "Vaccination and immunization", "vaccines", "Attenuated vaccines", "Immunity to infections", "Infectious diseases", "Viral diseases", "Respiratory syncytial virus infection", "bpze1", "phenotypic", "maturation", "rsv-infected"], "article_id"=>1085719, "categories"=>["Biological Sciences"], "users"=>["Ilaria Schiavoni", "Giorgio Fedele", "Adriano Quattrini", "Manuela Bianco", "Corinna Schnoeller", "Peter J. Openshaw", "Camille Locht", "Clara M. Ausiello"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100166.g001", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Impact_of_BPZE1_on_phenotypic_maturation_of_RSV_infected_MDDC_/1085719", "title"=>"Impact of BPZE1 on phenotypic maturation of RSV-infected MDDC.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-26 03:22:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/1568812"], "description"=>"<p>MDDC were treated with BPZE1 (100∶1), RSV (MOI of 1) or both. Mock-infected cells were added as control. Total RNA was extracted at the indicated time points. Kinetics of mRNA expression for p40 and p35 subunits of IL-12p70, IL-6, IFNβ and CCL5 was evaluated by real-time quantitative RT-PCR. The mRNA transcripts were normalized with respect to the endogenous reference (human β actin) sample. Data were expressed as fold increase (mean ± SEM of four experiments) with respect to mock-treated cells at 5 h.</p>", "links"=>[], "tags"=>["cell biology", "Cellular types", "Animal cells", "Immune cells", "Antigen-presenting cells", "Dendritic cells", "Signal transduction", "cell signaling", "Signaling cascades", "MAPK signaling cascades", "immunology", "Clinical immunology", "immunomodulation", "Vaccination and immunization", "vaccines", "Attenuated vaccines", "Immunity to infections", "Infectious diseases", "Viral diseases", "Respiratory syncytial virus infection", "bpze1-induced", "il-12p40", "il-12p35"], "article_id"=>1085732, "categories"=>["Biological Sciences"], "users"=>["Ilaria Schiavoni", "Giorgio Fedele", "Adriano Quattrini", "Manuela Bianco", "Corinna Schnoeller", "Peter J. Openshaw", "Camille Locht", "Clara M. Ausiello"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100166.g006", "stats"=>{"downloads"=>4, "page_views"=>78, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_RSV_and_BPZE1_induced_IL_6_IFN_946_CCL5_IL_12p40_and_IL_12p35_gene_expression_in_MDDC_/1085732", "title"=>"RSV- and BPZE1-induced IL-6, IFNβ, CCL5, IL-12p40 and IL-12p35 gene expression in MDDC.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-26 03:22:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/1568809"], "description"=>"<p><b>A</b>: Total cell lysates were prepared from MDDC treated with BPZE1 (100∶1), RSV (MOI of 1) or both at the indicated time-points. Mock-infected cells were added as control. Proteins were resolved by 10% SDS-PAGE and Western blot analysis was performed to detect the phosphorylation of STAT1, IkBα, ERK1/2 and p38. Human phosphorylated β actin was used to normalize the results. Data are from one representative of three independent experiments performed with MDDC obtained from different donors. <b>B</b>: Histograms represent means of the relative optical density of phosphorylated proteins from three independent experiments. Error bars represent SEM.</p>", "links"=>[], "tags"=>["cell biology", "Cellular types", "Animal cells", "Immune cells", "Antigen-presenting cells", "Dendritic cells", "Signal transduction", "cell signaling", "Signaling cascades", "MAPK signaling cascades", "immunology", "Clinical immunology", "immunomodulation", "Vaccination and immunization", "vaccines", "Attenuated vaccines", "Immunity to infections", "Infectious diseases", "Viral diseases", "Respiratory syncytial virus infection", "bpze1-induced", "pathways"], "article_id"=>1085729, "categories"=>["Biological Sciences"], "users"=>["Ilaria Schiavoni", "Giorgio Fedele", "Adriano Quattrini", "Manuela Bianco", "Corinna Schnoeller", "Peter J. Openshaw", "Camille Locht", "Clara M. Ausiello"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100166.g005", "stats"=>{"downloads"=>2, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_RSV_and_BPZE1_induced_signaling_pathways_in_MDDC_/1085729", "title"=>"RSV- and BPZE1-induced signaling pathways in MDDC.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-26 03:22:13"}

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Relative Metric

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