Systemic LPS Translocation Activates Cross-Presenting Dendritic Cells but Is Dispensable for the Breakdown of CD8+ T Cell Peripheral Tolerance in Irradiated Mice
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{"title"=>"Systemic LPS translocation activates cross-presenting dendritic cells but is dispensable for the breakdown of CD8+T cell peripheral tolerance in irradiated mice", "type"=>"journal", "authors"=>[{"first_name"=>"Gabriel", "last_name"=>"Espinosa-Carrasco", "scopus_author_id"=>"57045986400"}, {"first_name"=>"Marine", "last_name"=>"Villard", "scopus_author_id"=>"36769517900"}, {"first_name"=>"Cecile", "last_name"=>"Le Saout", "scopus_author_id"=>"36600768800"}, {"first_name"=>"Pascale", "last_name"=>"Louis-Plence", "scopus_author_id"=>"55996100200"}, {"first_name"=>"Rita", "last_name"=>"Vicente", "scopus_author_id"=>"8833627500"}, {"first_name"=>"Javier", "last_name"=>"Hernandez", "scopus_author_id"=>"25825149900"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84953897939", "doi"=>"10.1371/journal.pone.0130041", "issn"=>"19326203", "sgr"=>"84953897939", "pui"=>"605142863", "pmid"=>"26075613"}, "id"=>"71f8997a-f2ed-3d97-9326-db9d58becdc4", "abstract"=>"Lymphodepletion is currently used to enhance the efficacy of cytotoxic T lymphocyte adoptive transfer immunotherapy against cancer. This beneficial effect of conditioning regimens is due, at least in part, to promoting the breakdown of peripheral CD8+ T cell tolerance. Lymphodepletion by total body irradiation induces systemic translocation of commensal bacteria LPS from the gastrointestinal tract. Since LPS is a potent activator of the innate immune system, including antigen presenting dendritic cells, we hypothesized that LPS translocation could be required for the breakdown of peripheral tolerance observed in irradiated mice. To address this issue, we have treated irradiated mice with antibiotics in order to prevent LPS translocation and utilized them in T cell adoptive transfer experiments. Surprisingly, we found that despite of completely blocking LPS translocation into the bloodstream, antibiotic treatment did not prevent the breakdown of peripheral tolerance. Although irradiation induced the activation of cross-presenting CD8+ dendritic cells in the lymphoid tissue, LPS could not solely account for this effect. Activation of dendritic cells by mechanisms other than LPS translocation is sufficient to promote the differentiation of potentially autoreactive CD8+ T cells into effectors in irradiated mice. Our data indicate that LPS translocation is dispensable for the breakdown of CD8+ T cell tolerance in irradiated mice.", "link"=>"http://www.mendeley.com/research/systemic-lps-translocation-activates-crosspresenting-dendritic-cells-dispensable-breakdown-cd8t-cell", "reader_count"=>5, "reader_count_by_academic_status"=>{"Student > Doctoral Student"=>1, "Researcher"=>4}, "reader_count_by_user_role"=>{"Student > Doctoral Student"=>1, "Researcher"=>4}, "reader_count_by_subject_area"=>{"Agricultural and Biological Sciences"=>2, "Medicine and Dentistry"=>1, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2113515"], "description"=>"<p>BALB/c mice were sacrificed 24h after irradiation, non-irradiated mice served as controls, and T cells, NK cells, B cells, Monocyte/Macrophages and DCs were enumerated. Absolute numbers of CD3<sup>+</sup> CD8<sup>+</sup> T cells, CD3<sup>+</sup> CD4<sup>+</sup> T cells, CD3<sup>-</sup> DX5<sup>+</sup> NK cells, CD19<sup>+</sup> B cells, CD11b<sup>+</sup> F4/80<sup>+</sup> Mono/Macro, CD3<sup>-</sup> CD19<sup>-</sup> DX5<sup>-</sup> CD11c<sup>+</sup> MHC II<sup>+</sup> DC and CD3<sup>-</sup> CD19<sup>-</sup> DX5<sup>-</sup> CD11c<sup>+</sup> MHC II<sup>+</sup> CD8<sup>+</sup> DC in the LN are represented as means ± SD (n = 4–8) from two independent experiments out of four.</p>", "links"=>[], "tags"=>["LPS translocation", "cytotoxic T lymphocyte", "tolerance", "breakdown", "Irradiated Mice Lymphodepletion", "Dendritic cells", "commensal bacteria LPS"], "article_id"=>1449792, "categories"=>["Biological Sciences"], "users"=>["Gabriel Espinosa-Carrasco", "Marine Villard", "Cécile Le Saout", "Pascale Louis-Plence", "Rita Vicente", "Javier Hernandez"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130041.g001", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Depletion_of_immune_cell_populations_in_irradiated_BALB_c_mice_/1449792", "title"=>"Depletion of immune cell populations in irradiated BALB/c mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-15 03:28:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/2113522"], "description"=>"<p><b>(A)</b> Irradiated and antibiotic-treated irradiated groups of InsHA mice adoptively transferred with 5x10<sup>6</sup> CFSE-labeled naïve Clone 4 Thy1.1<sup>+</sup> CD8<sup>+</sup> and 5x10<sup>6</sup> HNT CD4<sup>+</sup> T cells were sacrificed on day 10 after transfer. CFSE fluorescence intensity on gated CD8<sup>+</sup> Thy1.1<sup>+</sup> donor lymphocytes in LN and pLN of single representative mice are shown in left and central panels. Percentages of highly proliferating cells, means ± SD (n = 4), of one experiment out three are presented. The presence of CD8<sup>+</sup> Thy1.1<sup>+</sup> donor T cells in the pancreas is shown in right panels. Numbers indicate FACS event counts in the depicted gates as means ± SD (n = 4) of one representative experiment out three. <b>(B)</b> Phenotype of CD8<sup>+</sup> Thy1.1<sup>+</sup> donor lymphocytes in the pLN of individual InsHA mice from groups described in panel A. Percentages of CD25<sup>+</sup> Granzyme B<sup>+</sup> of the donor T cells from pooled pLN of one experiment out of two.</p>", "links"=>[], "tags"=>["LPS translocation", "cytotoxic T lymphocyte", "tolerance", "breakdown", "Irradiated Mice Lymphodepletion", "Dendritic cells", "commensal bacteria LPS"], "article_id"=>1449799, "categories"=>["Biological Sciences"], "users"=>["Gabriel Espinosa-Carrasco", "Marine Villard", "Cécile Le Saout", "Pascale Louis-Plence", "Rita Vicente", "Javier Hernandez"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130041.g005", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Antibiotics_do_not_prevent_antigen_driven_proliferation_and_differentiation_of_Clone_4_CD8_T_cells_into_effectors_in_irradiated_InsHA_mice_/1449799", "title"=>"Antibiotics do not prevent antigen-driven proliferation and differentiation of Clone 4 CD8<sup>+</sup> T cells into effectors in irradiated InsHA mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-15 03:28:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/2113523", "https://ndownloader.figshare.com/files/2113524", "https://ndownloader.figshare.com/files/2113525", "https://ndownloader.figshare.com/files/2113526", "https://ndownloader.figshare.com/files/2113527", "https://ndownloader.figshare.com/files/2113528", "https://ndownloader.figshare.com/files/2113529", "https://ndownloader.figshare.com/files/2113530"], "description"=>"<div><p>Lymphodepletion is currently used to enhance the efficacy of cytotoxic T lymphocyte adoptive transfer immunotherapy against cancer. This beneficial effect of conditioning regimens is due, at least in part, to promoting the breakdown of peripheral CD8<sup>+</sup> T cell tolerance. Lymphodepletion by total body irradiation induces systemic translocation of commensal bacteria LPS from the gastrointestinal tract. Since LPS is a potent activator of the innate immune system, including antigen presenting dendritic cells, we hypothesized that LPS translocation could be required for the breakdown of peripheral tolerance observed in irradiated mice. To address this issue, we have treated irradiated mice with antibiotics in order to prevent LPS translocation and utilized them in T cell adoptive transfer experiments. Surprisingly, we found that despite of completely blocking LPS translocation into the bloodstream, antibiotic treatment did not prevent the breakdown of peripheral tolerance. Although irradiation induced the activation of cross-presenting CD8<sup>+</sup> dendritic cells in the lymphoid tissue, LPS could not solely account for this effect. Activation of dendritic cells by mechanisms other than LPS translocation is sufficient to promote the differentiation of potentially autoreactive CD8<sup>+</sup> T cells into effectors in irradiated mice. Our data indicate that LPS translocation is dispensable for the breakdown of CD8<sup>+</sup> T cell tolerance in irradiated mice.</p></div>", "links"=>[], "tags"=>["LPS translocation", "cytotoxic T lymphocyte", "tolerance", "breakdown", "Irradiated Mice Lymphodepletion", "Dendritic cells", "commensal bacteria LPS"], "article_id"=>1449800, "categories"=>["Biological Sciences"], "users"=>["Gabriel Espinosa-Carrasco", "Marine Villard", "Cécile Le Saout", "Pascale Louis-Plence", "Rita Vicente", "Javier Hernandez"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0130041.s001", "https://dx.doi.org/10.1371/journal.pone.0130041.s002", "https://dx.doi.org/10.1371/journal.pone.0130041.s003", "https://dx.doi.org/10.1371/journal.pone.0130041.s004", "https://dx.doi.org/10.1371/journal.pone.0130041.s005", "https://dx.doi.org/10.1371/journal.pone.0130041.s006", "https://dx.doi.org/10.1371/journal.pone.0130041.s007", "https://dx.doi.org/10.1371/journal.pone.0130041.s008"], "stats"=>{"downloads"=>5, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Systemic_LPS_Translocation_Activates_Cross_Presenting_Dendritic_Cells_but_Is_Dispensable_for_the_Breakdown_of_CD8_T_Cell_Peripheral_Tolerance_in_Irradiated_Mice/1449800", "title"=>"Systemic LPS Translocation Activates Cross-Presenting Dendritic Cells but Is Dispensable for the Breakdown of CD8<sup>+</sup> T Cell Peripheral Tolerance in Irradiated Mice", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-06-15 03:28:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/2113518"], "description"=>"<p><b>(A)</b> Non-irradiated, irradiated and antibiotic-treated irradiated groups of BALB/c mice have been described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0130041#pone.0130041.g002\" target=\"_blank\">Fig 2</a>. Mice were sacrificed 24h after irradiation and the expression of CD40, MHC class II, CD80 and CD86 on gated living CD3<sup>-</sup> CD19<sup>-</sup> DX5<sup>-</sup> CD11c<sup>+</sup> MHC II<sup>+</sup> DC from the LN was analyzed by FACS. Increase in MFI respect to isotype-matched controls is represented as means ± SD (n = 6–8) from two independent experiments out of four. <b>(B)</b> Histograms represent the phenotype of CD3<sup>-</sup> CD19<sup>-</sup> DX5<sup>-</sup> CD11c<sup>+</sup> MHC II<sup>+</sup> DC from individual representative mice described in panel A. <b>(C)</b> Non-irradiated and LPS-injected groups of mice described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0130041#pone.0130041.g002\" target=\"_blank\">Fig 2</a> were sacrificed 24 after treatment. Expression of CD40, MHC class II, CD80 and CD86 on gated living CD3<sup>-</sup> CD19<sup>-</sup> DX5<sup>-</sup> CD11c<sup>+</sup> MHC II<sup>+</sup> DC was analyzed by FACS. Increase in MFI respect to isotype-matched controls is represented as means ± SD (n = 3–4) from two independent experiments out of three.</p>", "links"=>[], "tags"=>["LPS translocation", "cytotoxic T lymphocyte", "tolerance", "breakdown", "Irradiated Mice Lymphodepletion", "Dendritic cells", "commensal bacteria LPS"], "article_id"=>1449795, "categories"=>["Biological Sciences"], "users"=>["Gabriel Espinosa-Carrasco", "Marine Villard", "Cécile Le Saout", "Pascale Louis-Plence", "Rita Vicente", "Javier Hernandez"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130041.g003", "stats"=>{"downloads"=>2, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Antibiotics_partially_block_irradiation_induced_activation_of_CD11c_DC_/1449795", "title"=>"Antibiotics partially block irradiation-induced activation of CD11c<sup>+</sup> DC.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-15 03:28:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/2113520"], "description"=>"<p><b>(A)</b> Non-irradiated, irradiated and antibiotic-treated irradiated groups of BALB/c mice have been described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0130041#pone.0130041.g002\" target=\"_blank\">Fig 2</a>. Mice were sacrificed 24h after irradiation and the expression of CD40, MHC class II, CD80 and CD86 on gated living CD3<sup>-</sup> CD19<sup>-</sup> DX5<sup>-</sup> CD11c<sup>+</sup> MHC II<sup>+</sup> CD8<sup>+</sup> DC from the LN was analyzed by FACS. Increase in MFI respect to isotype-matched controls is represented as means ± SD (n = 6–8) from two independent experiments out of four. <b>(B)</b> Histograms represent the phenotype of CD3<sup>-</sup> CD19<sup>-</sup> DX5<sup>-</sup> CD11c<sup>+</sup> MHC II<sup>+</sup> CD8<sup>+</sup> DC from individual representative mice described in panel A.</p>", "links"=>[], "tags"=>["LPS translocation", "cytotoxic T lymphocyte", "tolerance", "breakdown", "Irradiated Mice Lymphodepletion", "Dendritic cells", "commensal bacteria LPS"], "article_id"=>1449797, "categories"=>["Biological Sciences"], "users"=>["Gabriel Espinosa-Carrasco", "Marine Villard", "Cécile Le Saout", "Pascale Louis-Plence", "Rita Vicente", "Javier Hernandez"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130041.g004", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Antibiotics_partially_block_irradiation_induced_activation_of_CD8_DC_/1449797", "title"=>"Antibiotics partially block irradiation-induced activation of CD8<sup>+</sup> DC.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-15 03:28:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/2113516"], "description"=>"<p>Sera from BALB/c mice were collected 24h (IRR 24h) or 48h (IRR 48h) after irradiation. Antibiotic-treated BALB/c mice were irradiated 8 days later and sera collected 24h after irradiation (Antibx + IRR 24h). Sera collected 24h after Ultrapure LPS i.p. injection from non-irradiated BALB/c mice served as positive control (LPS 24h). Sera from non-irradiated mice served as negative control (Non IRR). Concentration of LBP in serum is presented as means ± SD (n = 4–7) from 3 independent experiments.</p>", "links"=>[], "tags"=>["LPS translocation", "cytotoxic T lymphocyte", "tolerance", "breakdown", "Irradiated Mice Lymphodepletion", "Dendritic cells", "commensal bacteria LPS"], "article_id"=>1449793, "categories"=>["Biological Sciences"], "users"=>["Gabriel Espinosa-Carrasco", "Marine Villard", "Cécile Le Saout", "Pascale Louis-Plence", "Rita Vicente", "Javier Hernandez"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130041.g002", "stats"=>{"downloads"=>4, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Irradiation_induced_systemic_LPS_translocation_is_prevented_by_antibiotics_in_BALB_c_mice_/1449793", "title"=>"Irradiation-induced systemic LPS translocation is prevented by antibiotics in BALB/c mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-15 03:28:39"}

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Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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