CCR2+ Inflammatory Dendritic Cells and Translocation of Antigen by Type III Secretion Are Required for the Exceptionally Large CD8+ T Cell Response to the Protective YopE69-77 Epitope during Yersinia Infection
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{"title"=>"CCR2+ Inflammatory Dendritic Cells and Translocation of Antigen by Type III Secretion Are Required for the Exceptionally Large CD8+ T Cell Response to the Protective YopE69-77 Epitope during Yersinia Infection", "type"=>"journal", "authors"=>[{"first_name"=>"Yue", "last_name"=>"Zhang", "scopus_author_id"=>"56227690300"}, {"first_name"=>"Jason W.", "last_name"=>"Tam", "scopus_author_id"=>"55331367400"}, {"first_name"=>"Patricio", "last_name"=>"Mena", "scopus_author_id"=>"16166898500"}, {"first_name"=>"Adrianus W.M.", "last_name"=>"van der Velden", "scopus_author_id"=>"36515946800"}, {"first_name"=>"James B.", "last_name"=>"Bliska", "scopus_author_id"=>"7004681489"}], "year"=>2015, "source"=>"PLoS Pathogens", "identifiers"=>{"isbn"=>"1553-7374 (Electronic)\\r1553-7366 (Linking)", "pmid"=>"26468944", "doi"=>"10.1371/journal.ppat.1005167", "pui"=>"606741180", "issn"=>"15537374", "sgr"=>"84946098333", "scopus"=>"2-s2.0-84946098333"}, "id"=>"bea1c4b3-84b5-3291-8e55-a85fa706390e", "abstract"=>"During Yersinia pseudotuberculosis infection of C57BL/6 mice, an exceptionally large CD8+ T cell response to a protective epitope in the type III secretion system effector YopE is produced. At the peak of the response, up to 50% of splenic CD8+ T cells recognize the epitope YopE69-77. The features of the interaction between pathogen and host that result in this large CD8+ T cell response are unknown. Here, we used Y. pseudotuberculosis strains defective for production, secretion and/or translocation of YopE to infect wild-type or mutant mice deficient in specific dendritic cells (DCs). Bacterial colonization of organs and translocation of YopE into spleen cells was measured, and flow cytometry and tetramer staining were used to characterize the cellular immune response. We show that the splenic YopE69-77-specific CD8+ T cells generated during the large response are polyclonal and are produced by a \"translocation-dependent\" pathway that requires injection of YopE into host cell cytosol. Additionally, a smaller YopE69-77-specific CD8+ T cell response (~10% of the large expansion) can be generated in a \"translocation-independent\" pathway in which CD8alpha+ DCs cross present secreted YopE. CCR2-expressing inflammatory DCs were required for the large YopE69-77-specific CD8+ T cell expansion because this response was significantly reduced in Ccr2-/- mice, YopE was translocated into inflammatory DCs in vivo, inflammatory DCs purified from infected spleens activated YopE69-77-specific CD8+ T cells ex vivo and promoted the expansion of YopE69-77-specific CD8+ T cells in infected Ccr2-/- mice after adoptive transfer. A requirement for inflammatory DCs in producing a protective CD8+ T cell response to a bacterial antigen has not previously been demonstrated. Therefore, the production of YopE69-77-specific CD8+ T cells by inflammatory DCs that are injected with YopE during Y. pseudotuberculosis infection represents a novel mechanism for generating a massive and protective adaptive immune response.", "link"=>"http://www.mendeley.com/research/ccr2-inflammatory-dendritic-cells-translocation-antigen-type-iii-secretion-required-exceptionally-la", "reader_count"=>9, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>2, "Student > Master"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>2, "Student > Master"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Agricultural and Biological Sciences"=>3, "Medicine and Dentistry"=>1, "Immunology and Microbiology"=>4}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Unspecified"=>{"Unspecified"=>1}}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2360996"], "description"=>"<p>C57BL/6 or C57BL/6 Batf3<sup>-/-</sup> mice were left uninfected (UI) or infected IV with 1000 CFU of mE or 5X10<sup>5</sup> CFU of ΔBmE. Spleen (A) and liver (B) colonization levels were determined by CFU assay on 7 dpi. The number of splenic CD8<sup>+</sup> T cells (C) and ET cells (D) was determined by flow cytometry following tetramer and CD8α staining. Data shown are the summary of two or more independent experiments. Non-colonized mice were removed from analysis and P values were determined with the Mann-Whitney test.</p>", "links"=>[], "tags"=>["ccr", "novel mechanism", "Bacterial colonization", "pseudotuberculosis infection", "pseudotuberculosis strains", "flow cytometry", "tetramer staining", "Yersinia infection", "dc", "C 57BL mice", "Yersinia pseudotuberculosis infection", "host cell cytosol", "response", "type III secretion system effector YopE", "Dendritic cells", "spleen cells", "type III secretion"], "article_id"=>1576565, "categories"=>["Biological Sciences"], "users"=>["Yue Zhang", "Jason W. Tam", "Patricio Mena", "Adrianus W. M. van der Velden", "James B. Bliska"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005167.g004", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Diminished_translocation_independent_production_of_ET_cells_in_Batf3_mice_/1576565", "title"=>"Diminished translocation-independent production of ET cells in Batf3<sup>-/-</sup> mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-15 02:53:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/2360995"], "description"=>"<p>Groups of C57BL/6 mice were infected IV with 1000 CFU of mE, 5X10<sup>5</sup> CFU of ΔBmE, 1X10<sup>5</sup> to 1X10<sup>6</sup> CFU of ΔYscF or 1000 CFU of YopEΔN15 or ΔYopE or left uninfected (UI). The colonization levels in spleen (A) or liver (B) were determined by CFU assay 7 dpi. The detection limit of log<sub>10</sub>CFU = 1.7 is indicated with dotted line. (C) Representative histographs of CD8α and YopE<sub>69-77</sub> tetramer signals on splenocytes from mice infected for 7 days with mE, ΔBmE, ΔYscF, YopEΔN15 or ΔYopE as indicated, with the percentage of ET cells in splenocytes indicated with oval gates. The number of splenic ET cells (D) and CD8<sup>+</sup> T cells (E) in groups of mice at 7 dpi was determined by flow cytometry following tetramer and antibody staining. Each symbol represents the value obtained from one mouse. Data shown are the summary of two to four independent experiments. P values obtained with the Mann-Whitney test are shown when the values are statistically different between the indicated groups (A, B and E). In D, the values obtained from mice infected with mE or ΔBmE are significantly different from all others and are indicated with *** for P<0.001 and ** for P<0.01.</p>", "links"=>[], "tags"=>["ccr", "novel mechanism", "Bacterial colonization", "pseudotuberculosis infection", "pseudotuberculosis strains", "flow cytometry", "tetramer staining", "Yersinia infection", "dc", "C 57BL mice", "Yersinia pseudotuberculosis infection", "host cell cytosol", "response", "type III secretion system effector YopE", "Dendritic cells", "spleen cells", "type III secretion"], "article_id"=>1576564, "categories"=>["Biological Sciences"], "users"=>["Yue Zhang", "Jason W. Tam", "Patricio Mena", "Adrianus W. M. van der Velden", "James B. Bliska"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005167.g003", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Translocation_dependent_and_independent_production_of_ET_cells_/1576564", "title"=>"Translocation-dependent and-independent production of ET cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-15 02:53:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/2360990"], "description"=>"<p>Splenocytes from C57BL/6 mice infected IV with <i>Y</i>. <i>pseudotuberculosis</i> mE for 7 days (A and filled circles in B) or one year (empty circles in B) were stained with YopE<sub>69-77</sub> tetramer, a panel of Vβ antibodies and CD8 antibody conjugated with different fluorophores and were analyzed by flow cytometry. Representative histographs of tetramer (YopE-APC) and Vβ8.1 & 8.2 (left) or Vβ8.3 (right) signals from CD8<sup>+</sup> T cells from one mouse are shown in (A). Numerical values correspond to percentages of gated cell populations among total CD8<sup>+</sup> T cells. A summary of the percentages of each Vβ subset of total Vβ (% total) among ET cells from 3 mice infected for 7 days and 2 mice infected for 1 year is shown in (B). Mean and SEM is shown for each group of 5 mice.</p>", "links"=>[], "tags"=>["ccr", "novel mechanism", "Bacterial colonization", "pseudotuberculosis infection", "pseudotuberculosis strains", "flow cytometry", "tetramer staining", "Yersinia infection", "dc", "C 57BL mice", "Yersinia pseudotuberculosis infection", "host cell cytosol", "response", "type III secretion system effector YopE", "Dendritic cells", "spleen cells", "type III secretion"], "article_id"=>1576559, "categories"=>["Biological Sciences"], "users"=>["Yue Zhang", "Jason W. Tam", "Patricio Mena", "Adrianus W. M. van der Velden", "James B. Bliska"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005167.g001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TCR_V_946_subset_distribution_in_ET_cells_/1576559", "title"=>"TCR Vβ subset distribution in ET cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-15 02:53:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/2360992"], "description"=>"<p>The indicated strains of <i>Y</i>. <i>pseudotuberculosis</i> were grown at 37°C in LB containing 2.5 mM of CaCl<sub>2</sub> (High Ca<sup>2+</sup>) to inhibit type III secretion (A), or in LB containing 20 mM MgCl and 20 mM NaOX (Low Ca<sup>2+</sup>) to activate type III secretion (B). Lysates of the bacteria were subjected to immunoblotting with anti-YopE antibodies. Immunoblotting with anti-DnaK antibody was used to indicate equal loading. (C) The indicated strains grown at 37°C in low Ca<sup>2+</sup> LB were used to infect BMDMs at a MOI of 50 for 1.5 h. The infected BMDMs were incubated with a non-iononic detergent buffer and then separated into an insoluble fraction containing bacteria or a soluble fraction containing cytosolic components. Samples of the insoluble (left panel) or soluble (right panel) fractions were subjected to immunoblotting with anti-YopE antibody or anti-β-actin antibody to control for loading. Results shown are representative of three independent experiments. (D) The indicated strains were added to wells without BMDMs or to wells containing BMDMs at MOI of 10 for 4 h, and gentamicin was included during the last 2 h. Then ET-enriched CD8<sup>+</sup> T cell lines in medium containing penicillin and streptomycin were added to wells containing bacteria alone or to wells containing BMDMs infected with bacteria at 1:4 (BMDM to T cell) ratio and incubated for 48 h before measuring the concentration of IFNγ in the supernatants by ELISA. Data shown are results from one representative of 4 experiments performed.</p>", "links"=>[], "tags"=>["ccr", "novel mechanism", "Bacterial colonization", "pseudotuberculosis infection", "pseudotuberculosis strains", "flow cytometry", "tetramer staining", "Yersinia infection", "dc", "C 57BL mice", "Yersinia pseudotuberculosis infection", "host cell cytosol", "response", "type III secretion system effector YopE", "Dendritic cells", "spleen cells", "type III secretion"], "article_id"=>1576560, "categories"=>["Biological Sciences"], "users"=>["Yue Zhang", "Jason W. Tam", "Patricio Mena", "Adrianus W. M. van der Velden", "James B. Bliska"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005167.g002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Measurement_of_production_translocation_and_antigen_presentation_of_YopE_in_vitro_/1576560", "title"=>"Measurement of production, translocation and antigen presentation of YopE in vitro.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-15 02:53:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/2361004"], "description"=>"<p><i>Y</i>. <i>pseudotuberculosis</i> strains used in the study.</p>", "links"=>[], "tags"=>["ccr", "novel mechanism", "Bacterial colonization", "pseudotuberculosis infection", "pseudotuberculosis strains", "flow cytometry", "tetramer staining", "Yersinia infection", "dc", "C 57BL mice", "Yersinia pseudotuberculosis infection", "host cell cytosol", "response", "type III secretion system effector YopE", "Dendritic cells", "spleen cells", "type III secretion"], "article_id"=>1576573, "categories"=>["Biological Sciences"], "users"=>["Yue Zhang", "Jason W. Tam", "Patricio Mena", "Adrianus W. M. van der Velden", "James B. Bliska"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005167.t001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Y_pseudotuberculosis_strains_used_in_the_study_/1576573", "title"=>"<i>Y</i>. <i>pseudotuberculosis</i> strains used in the study.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-10-15 02:53:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/2361003"], "description"=>"<p>(A and B) CCR2-GFP mice were infected IV with 1000 CFU of mE or 5X10<sup>5</sup> CFU of ΔBmE, and 7 days later, total monocytes from spleens were isolated by negative selection. GFP<sup>+</sup> cells were sorted from the GFP<sup>-</sup> cells and characterized using flow cytometry (A, dark and light green lines representing cells from mice infected with mE orΔBmE, respectively). Results shown are representative of two independent experiments performed. After incubating the indicated GFP<sup>+</sup> or GFP<sup>-</sup> subpopulations with ET-enriched CD8<sup>+</sup> T cells for 48 h, the concentrations of IFNγ were determined (B). The average concentration of IFNγ from samples obtained with GPF<sup>+</sup> cells isolated from mE-infected mice was set at 100%, and the other values were normalized accordingly within the same experiment. The results shown in (B) are a summary of two experiments performed with a total of 3 mice infected with mE and 2 mice infected with ΔBmE. P value was determined with one way ANOVA (Kruskal-Wallis Test) followed by Dunn’s Multiple Comparison Test. (C) Four days post IV infection of CCR2-GFP mice with 1000 CFU of ΔYopE, GFP<sup>+</sup> cells were enriched and sorted. PBS (PBS) or 1.8-2X10<sup>6</sup> GFP<sup>+</sup> (GFP) cells were injected to Ccr2<sup>-/-</sup> mice that were infected with 1000 CFU of mE the day before. Six days later or 7 dpi, the percentages of ET cells among all CD8<sup>+</sup> T cells were determined. By Mann-Whitney test, P = 0.02. Each symbol represented the value obtained from one mouse and the results shown are the summary of three independent experiments.</p>", "links"=>[], "tags"=>["ccr", "novel mechanism", "Bacterial colonization", "pseudotuberculosis infection", "pseudotuberculosis strains", "flow cytometry", "tetramer staining", "Yersinia infection", "dc", "C 57BL mice", "Yersinia pseudotuberculosis infection", "host cell cytosol", "response", "type III secretion system effector YopE", "Dendritic cells", "spleen cells", "type III secretion"], "article_id"=>1576572, "categories"=>["Biological Sciences"], "users"=>["Yue Zhang", "Jason W. Tam", "Patricio Mena", "Adrianus W. M. van der Velden", "James B. Bliska"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005167.g007", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Phenotypic_characterization_of_CCR2_expressing_infDCs_and_their_analysis_by_DEAD_assay_and_adoptive_transfer_/1576572", "title"=>"Phenotypic characterization of CCR2-expressing infDCs and their analysis by DEAD assay and adoptive transfer.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-15 02:53:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/2361000"], "description"=>"<p>C57BL/6 mice were IV infected with 10<sup>5</sup> CFU of YopE-Bla or 5X10<sup>6</sup> CFU of ΔB YopE-Bla for 6 days. Splenocytes isolated from surviving mice were incubated with CCF4-AM to detect the presence of translocated YopE-TEM1, and subsequently stained with a panel of antibodies and analyzed with flow cytometry. (A) A representative histograph of splenocytes from a mouse infected with YopE-Bla showing the gate for translocation positive cells (Blue). (B) Spleen and liver colonization levels were determined by CFU assay for YopE-Bla, and ΔB YopE-Bla and the combined value of spleen and liver colonization was plotted against the percentage of blue splenocytes in the same mice. Data shown are the summary of four independent experiments. (C) Splenocytes from mice infected with YopE-Bla for 6 days were analyzed by flow cytometry and the percentage of splenocytes positive for the indicated markers (top) and blue cells among these cells (bottom) were determined. (D) Percentage of Ly6C<sup>hi</sup> infDCs or Ly6C<sup>med</sup> PMNs among the CD11b<sup>+</sup> splenocytes from mice infected with YopE-Bla for 6 days were determined by flow cytometry (top), and the percentage of blue cells among these were plotted at bottom. Representative histograph of overlaid blue signal strength of PMNs (E) or infDC (F) from an individual mouse infected for 6 days with YopE-Bla (black lines) or ΔB YopE-Bla (light gray lines). The percentage of blue cells from the YopE-Bla-infected sample was indicated in the gate. In B-D, each dot represents the value obtained from one mouse, and wherever applicable, the bar indicated the average.</p>", "links"=>[], "tags"=>["ccr", "novel mechanism", "Bacterial colonization", "pseudotuberculosis infection", "pseudotuberculosis strains", "flow cytometry", "tetramer staining", "Yersinia infection", "dc", "C 57BL mice", "Yersinia pseudotuberculosis infection", "host cell cytosol", "response", "type III secretion system effector YopE", "Dendritic cells", "spleen cells", "type III secretion"], "article_id"=>1576569, "categories"=>["Biological Sciences"], "users"=>["Yue Zhang", "Jason W. Tam", "Patricio Mena", "Adrianus W. M. van der Velden", "James B. Bliska"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005167.g006", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Detection_of_YopE_TEM1_translocation_into_different_splenocyte_populations_/1576569", "title"=>"Detection of YopE-TEM1 translocation into different splenocyte populations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-15 02:53:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/2360998"], "description"=>"<p>Age and sex-matched C57BL/6 (filled symbols) or C57BL/6 Ccr2<sup>-/-</sup> mice (open symbols) were left uninfected or infected IV with 1000 CFU of mE (circles) or 5X10<sup>5</sup> CFU of ΔBmE (squares). Mouse survival (A) and weight (B) following infection with mE were monitored for 14 days. Data shown in (A) and (B) are from 1 experiment with 6 mice in each condition. Difference in survival was significant as determined with Log rank test. The differences in weight between the two groups of mice at different days were determined with two-way ANOVA followed by Bonferroni posttest. *, P<0.05; ***, P<0.001. (C) At different dpi as indicated with mE or 7 dpi with ΔBmE, spleen colonization levels were determined by CFU assay. (D) Representative histographs of Ly6C and CD11b signals on splenocytes from uninfected (UI) or mE-infected C57BL/6 or Ccr2<sup>-/-</sup> mice at 7 dpi, and the CD11b<sup>+</sup>Ly6C<sup>hi</sup> cells are indicated with an oval gate (percentage of total splenocytes within gate is shown). (E) The number of ET cells at 7 dpi was determined by flow cytometry following tetramer staining. Data shown in (C) and (E) are the summary of several independent experiments with at least two experiments at each time point. P values were determined with Mann-Whitney test as indicated in (C) or (E).</p>", "links"=>[], "tags"=>["ccr", "novel mechanism", "Bacterial colonization", "pseudotuberculosis infection", "pseudotuberculosis strains", "flow cytometry", "tetramer staining", "Yersinia infection", "dc", "C 57BL mice", "Yersinia pseudotuberculosis infection", "host cell cytosol", "response", "type III secretion system effector YopE", "Dendritic cells", "spleen cells", "type III secretion"], "article_id"=>1576567, "categories"=>["Biological Sciences"], "users"=>["Yue Zhang", "Jason W. Tam", "Patricio Mena", "Adrianus W. M. van der Velden", "James B. Bliska"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005167.g005", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CCR2_is_required_for_host_survival_and_the_large_translocation_dependent_ET_cell_response_/1576567", "title"=>"CCR2 is required for host survival and the large translocation-dependent ET cell response.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-15 02:53:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/2361008", "https://ndownloader.figshare.com/files/2361009", "https://ndownloader.figshare.com/files/2361010", "https://ndownloader.figshare.com/files/2361011", "https://ndownloader.figshare.com/files/2361012"], "description"=>"<div><p>During <i>Yersinia pseudotuberculosis</i> infection of C57BL/6 mice, an exceptionally large CD8<sup>+</sup> T cell response to a protective epitope in the type III secretion system effector YopE is produced. At the peak of the response, up to 50% of splenic CD8<sup>+</sup> T cells recognize the epitope YopE<sub>69-77</sub>. The features of the interaction between pathogen and host that result in this large CD8<sup>+</sup> T cell response are unknown. Here, we used <i>Y</i>. <i>pseudotuberculosis</i> strains defective for production, secretion and/or translocation of YopE to infect wild-type or mutant mice deficient in specific dendritic cells (DCs). Bacterial colonization of organs and translocation of YopE into spleen cells was measured, and flow cytometry and tetramer staining were used to characterize the cellular immune response. We show that the splenic YopE<sub>69-77</sub>-specific CD8<sup>+</sup> T cells generated during the large response are polyclonal and are produced by a “translocation-dependent” pathway that requires injection of YopE into host cell cytosol. Additionally, a smaller YopE<sub>69-77</sub>-specific CD8<sup>+</sup> T cell response (~10% of the large expansion) can be generated in a “translocation-independent” pathway in which CD8α<sup>+</sup> DCs cross present secreted YopE. CCR2-expressing inflammatory DCs were required for the large YopE<sub>69-77</sub>-specific CD8<sup>+</sup> T cell expansion because this response was significantly reduced in Ccr2<sup>-/-</sup> mice, YopE was translocated into inflammatory DCs in vivo, inflammatory DCs purified from infected spleens activated YopE<sub>69-77</sub>-specific CD8<sup>+</sup> T cells ex vivo and promoted the expansion of YopE<sub>69-77</sub>-specific CD8<sup>+</sup> T cells in infected Ccr2<sup>-/-</sup> mice after adoptive transfer. A requirement for inflammatory DCs in producing a protective CD8<sup>+</sup> T cell response to a bacterial antigen has not previously been demonstrated. Therefore, the production of YopE<sub>69-77</sub>-specific CD8<sup>+</sup> T cells by inflammatory DCs that are injected with YopE during <i>Y</i>. <i>pseudotuberculosis</i> infection represents a novel mechanism for generating a massive and protective adaptive immune response.</p></div>", "links"=>[], "tags"=>["ccr", "novel mechanism", "Bacterial colonization", "pseudotuberculosis infection", "pseudotuberculosis strains", "flow cytometry", "tetramer staining", "Yersinia infection", "dc", "C 57BL mice", "Yersinia pseudotuberculosis infection", "host cell cytosol", "response", "type III secretion system effector YopE", "Dendritic cells", "spleen cells", "type III secretion"], "article_id"=>1576575, "categories"=>["Biological Sciences"], "users"=>["Yue Zhang", "Jason W. Tam", "Patricio Mena", "Adrianus W. M. van der Velden", "James B. Bliska"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1005167.s001", "https://dx.doi.org/10.1371/journal.ppat.1005167.s002", "https://dx.doi.org/10.1371/journal.ppat.1005167.s003", "https://dx.doi.org/10.1371/journal.ppat.1005167.s004", "https://dx.doi.org/10.1371/journal.ppat.1005167.s005"], "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/CCR2_Inflammatory_Dendritic_Cells_and_Translocation_of_Antigen_by_Type_III_Secretion_Are_Required_for_the_Exceptionally_Large_CD8_T_Cell_Response_to_the_Protective_YopE_69_77_Epitope_during_Yersinia_Infection/1576575", "title"=>"CCR2<sup>+</sup> Inflammatory Dendritic Cells and Translocation of Antigen by Type III Secretion Are Required for the Exceptionally Large CD8<sup>+</sup> T Cell Response to the Protective YopE<sub>69-77</sub> Epitope during <i>Yersinia</i> Infection", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-10-15 02:53:20"}

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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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