Critical Role of IRF-5 in the Development of T helper 1 responses to Leishmania donovani infection
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{"title"=>"Critical role of IRF-5 in the development of t helper 1 responses to Leishmania donovani infection", "type"=>"journal", "authors"=>[{"first_name"=>"Andrea", "last_name"=>"Paun", "scopus_author_id"=>"15760588600"}, {"first_name"=>"Rashmi", "last_name"=>"Bankoti", "scopus_author_id"=>"36647383800"}, {"first_name"=>"Trupti", "last_name"=>"Joshi", "scopus_author_id"=>"57196973110"}, {"first_name"=>"Paula M.", "last_name"=>"Pitha", "scopus_author_id"=>"7103278680"}, {"first_name"=>"Simona", "last_name"=>"Stäger", "scopus_author_id"=>"7003294944"}], "year"=>2011, "source"=>"PLoS Pathogens", "identifiers"=>{"pui"=>"361204779", "issn"=>"15537366", "isbn"=>"1553-7374 (Electronic)\\n1553-7366 (Linking)", "doi"=>"10.1371/journal.ppat.1001246", "scopus"=>"2-s2.0-79551508963", "pmid"=>"21253574", "sgr"=>"79551508963"}, "id"=>"0b5d171c-2a72-32eb-8aae-3ccb510a8a39", "abstract"=>"The transcription factor Interferon Regulatory Factor 5 (IRF-5) has been shown to be involved in the induction of proinflammatory cytokines in response to viral infections and TLR activation and to play an essential role in the innate inflammatory response. In this study, we used the experimental model of visceral leishmaniasis to investigate the role of IRF-5 in the generation of Th1 responses and in the formation of Th1-type liver granulomas in Leishmania donovani infected mice. We show that TLR7-mediated activation of IRF-5 is essential for the development of Th1 responses to L. donovani in the spleen during chronic infection. We also demonstrate that IRF-5 deficiency leads to the incapacity to control L. donovani infection in the liver and to the formation of smaller granulomas. Granulomas in Irf5⁻/⁻ mice are characterized by an increased IL-4 and IL-10 response and concomitant low iNOS expression. Collectively, these results identify IRF-5 as a critical molecular switch for the development of Th1 immune responses following L. donovani infections and reveal an indirect role of IRF-5 in the regulation of iNOS expression.", "link"=>"http://www.mendeley.com/research/critical-role-irf5-development-t-helper-1-responses-leishmania-donovani-infection", "reader_count"=>48, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>3, "Researcher"=>8, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>17, "Student > Postgraduate"=>1, "Other"=>2, "Student > Master"=>7, "Student > Bachelor"=>4, "Professor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>3, "Researcher"=>8, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>17, "Student > Postgraduate"=>1, "Other"=>2, "Student > Master"=>7, "Student > Bachelor"=>4, "Professor"=>2}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>2, "Materials Science"=>1, "Mathematics"=>1, "Agricultural and Biological Sciences"=>28, "Medicine and Dentistry"=>8, "Veterinary Science and Veterinary Medicine"=>1, "Immunology and Microbiology"=>7}, "reader_count_by_subdiscipline"=>{"Materials Science"=>{"Materials Science"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>7}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>28}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Mathematics"=>{"Mathematics"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"Netherlands"=>1, "United States"=>2, "Brazil"=>1, "United Kingdom"=>1, "France"=>1, "Germany"=>1}, "group_count"=>2}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/808164"], "description"=>"<p>WT and <i>Irf5</i><sup>-/-</sup> mice were infected with <i>L. donovani</i> amistigotes. At 5 h, splenic cDCs were purified. IL-12p35 mRNA was detected by real time PCR. Data is shown for n = 3 WT samples and n = 4 <i>Irf5</i><sup>-/-</sup> samples.* denotes <i>p</i><0.05 and ** denotes <i>p</i><0.01.</p>", "links"=>[], "tags"=>["fails", "induce", "il-12p35"], "article_id"=>478535, "categories"=>["Immunology", "Medicine", "Physics"], "users"=>["Andrea Paun", "Rashmi Bankoti", "Trupti Joshi", "Paula M. Pitha", "Simona Stäger"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1001246.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_L_donovani_fails_to_induce_IL_12p35_expression_in_Irf5_mice_/478535", "title"=>"<i>L. donovani</i> fails to induce IL-12p35 expression in <i>Irf5<sup>-/-</sup></i> mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-01-06 02:22:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/808229"], "description"=>"<p>Real time PCR analysis of livers from infected mice measuring mRNA for iNOS (A), arginase1 (B) and Fizz1 (C). All data is presented as the mean ± SEM combined from two independent experiments, n = 6-9 mice per group. (D) iNOS protein in the liver was examined by immunohistochemistry. (E) Induction of the <i>NOS2</i> promoter by MyD88 and IRF-5 was measured by luciferase assay. Data shown is fold induction of the promoter compared to promoter only controls and represents the mean± SEM for triplicate samples from 2 independent experiments. * denotes <i>p</i><0.05 and ** denotes <i>p</i><0.01. (F) Real time PCR analysis of iNOS mRNA in WT and Irf5-/- macrophages stimulated with LPS and/or <i>L.donovani</i> amastigotes. Data is shown for n = 3.</p>", "links"=>[], "tags"=>["deficiency", "defective", "inos"], "article_id"=>478598, "categories"=>["Immunology", "Medicine", "Physics"], "users"=>["Andrea Paun", "Rashmi Bankoti", "Trupti Joshi", "Paula M. Pitha", "Simona Stäger"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1001246.g005", "stats"=>{"downloads"=>2, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_IRF_5_deficiency_results_in_defective_iNOS_production_/478598", "title"=>"IRF-5 deficiency results in defective iNOS production.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-01-06 02:23:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/808011"], "description"=>"<p>The percentage of CD4<sup>+</sup> T cells producing IFNγ as a response to <i>L. donovani</i> infection in the liver (A) and the spleen (C) of WT and <i>Irf5</i><sup>-/-</sup> mice was determined by intracellular flow cytometry. Representative scatter plots from WT and <i>Irf5</i><sup>-/-</sup> mice infected with <i>L. donovani</i> showing IFNγ production by CD4<sup>+</sup> T cells in the liver (B) and spleen (D) at different times p.i.. Data is shown as the mean ± SEM. Flow cytometry data is representative of two independent experiments. * denotes <i>p</i><0.05 and ** denotes <i>p</i><0.01.</p>", "links"=>[], "tags"=>["mice", "defective", "th1"], "article_id"=>478375, "categories"=>["Immunology", "Medicine", "Physics"], "users"=>["Andrea Paun", "Rashmi Bankoti", "Trupti Joshi", "Paula M. Pitha", "Simona Stäger"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1001246.g002", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Irf5_mice_have_a_defective_Th1_response_/478375", "title"=>"<i>Irf5</i><sup>-/-</sup> mice have a defective Th1 response.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-01-06 02:19:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/807958"], "description"=>"<p>Parasite burdens in the spleen (A) and liver (B) were determined for infected WT and <i>Irf5</i><sup>-/-</sup> mice at d14 and d28 pi as described. Data shown is the mean ± SEM and is representative of two independent experiments. * denotes <i>p</i><0.05 and ** denotes <i>p</i><0.01.</p>", "links"=>[], "tags"=>["immunology/immune response", "immunology/immunity to infections", "immunology/innate immunity", "infectious diseases/neglected tropical diseases", "infectious diseases/protozoal infections"], "article_id"=>478320, "categories"=>["Immunology", "Medicine", "Physics"], "users"=>["Andrea Paun", "Rashmi Bankoti", "Trupti Joshi", "Paula M. Pitha", "Simona Stäger"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1001246.g001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Leishmania_donovani_infection_in_Irf5_mice_/478320", "title"=>"<i>Leishmania donovani</i> infection in <i>Irf5</i><sup>-/-</sup> mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-01-06 02:18:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/403265", "https://ndownloader.figshare.com/files/403299", "https://ndownloader.figshare.com/files/403320"], "description"=>"<div><p>The transcription factor Interferon Regulatory Factor 5 (IRF-5) has been shown to be involved in the induction of proinflammatory cytokines in response to viral infections and TLR activation and to play an essential role in the innate inflammatory response. In this study, we used the experimental model of visceral leishmaniasis to investigate the role of IRF-5 in the generation of Th1 responses and in the formation of Th1-type liver granulomas in <em>Leishmania donovani</em> infected mice. We show that TLR7-mediated activation of IRF-5 is essential for the development of Th1 responses to <em>L. donovani</em> in the spleen during chronic infection. We also demonstrate that IRF-5 deficiency leads to the incapacity to control <em>L. donovani</em> infection in the liver and to the formation of smaller granulomas. Granulomas in <em>Irf5<sup>-/-</sup></em> mice are characterized by an increased IL-4 and IL-10 response and concomitant low iNOS expression. Collectively, these results identify IRF-5 as a critical molecular switch for the development of Th1 immune responses following <em>L. donovani</em> infections and reveal an indirect role of IRF-5 in the regulation of iNOS expression.</p></div>", "links"=>[], "tags"=>["irf-5", "helper", "responses"], "article_id"=>139677, "categories"=>["Immunology", "Medicine", "Physics"], "users"=>["Andrea Paun", "Rashmi Bankoti", "Trupti Joshi", "Paula M. Pitha", "Simona Stäger"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1001246.s001", "https://dx.doi.org/10.1371/journal.ppat.1001246.s002", "https://dx.doi.org/10.1371/journal.ppat.1001246.s003"], "stats"=>{"downloads"=>2, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Critical_Role_of_IRF_5_in_the_Development_of_T_helper_1_responses_to_Leishmania_donovani_infection/139677", "title"=>"Critical Role of IRF-5 in the Development of T helper 1 responses to <em>Leishmania donovani</em> infection", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-01-06 02:41:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/808375"], "description"=>"<p>(A) The hepatic parasite burden was determined for infected WT and <i>Tlr7</i><sup>-/-</sup> mice at d14 and d28 pi as described. (B) The percentage of CD4<sup>+</sup> T cells producing IFNγ as a response to <i>L. donovani</i> infection in the liver of WT and <i>Tlr7</i><sup>-/-</sup> mice was determined by intracellular flow cytometry. (C) Percentage of IFNγ<sup>+</sup> CD4<sup>+</sup> T-cells in the liver and (D) the spleen of WT and <i>Irf7<sup>-/-</sup></i> mice. (E,F) Real time PCR analysis of spleens (E) and livers (F) from infected WT and <i>Irf7<sup>-/-</sup></i> mice measuring mRNA for IRF5. Data is shown as the mean ± SEM. Data is representative of two independent experiments.</p>", "links"=>[], "tags"=>["activation", "th1", "responses"], "article_id"=>478745, "categories"=>["Immunology", "Medicine", "Physics"], "users"=>["Andrea Paun", "Rashmi Bankoti", "Trupti Joshi", "Paula M. Pitha", "Simona Stäger"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1001246.g007", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TLR7_activation_is_essential_for_the_development_of_Th1_responses_following_L_donovani_infection_/478745", "title"=>"TLR7 activation is essential for the development of Th1 responses following <i>L. donovani</i> infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-01-06 02:25:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/808087"], "description"=>"<p>(A) Representative granulomas from H&E stained liver sections at d28 pi in WT and <i>Irf5</i><sup>-/-</sup> mice. Pictures were taken at the indicated magnifications and arrows indicate the presence of neutrophils in the granulomas. (B, C) Real time PCR analysis of the livers (B) and spleen (C) measuring mRNA for CXCL1. (D) Spleen weights at d14 and d28 pi. The body weight of C57BL/6 WT and <i>Irf5<sup>-/-</sup></i> mice was comparable. (E) Real time PCR analysis of the livers from infected mice measuring mRNA for IL-23 p19. (F) Real time PCR measurement of cytokine mRNA in the livers of infected mice indicates a skewing toward a Th2 environment. All data is presented as the mean ± SEM combined from two independent experiments. * denotes <i>p</i><0.05 and ** denotes <i>p</i><0.01.</p>", "links"=>[], "tags"=>["mice", "th1-type"], "article_id"=>478455, "categories"=>["Immunology", "Medicine", "Physics"], "users"=>["Andrea Paun", "Rashmi Bankoti", "Trupti Joshi", "Paula M. Pitha", "Simona Stäger"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1001246.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Irf5_mice_do_not_develop_Th1_type_granulomas_/478455", "title"=>"<i>Irf5</i><sup>-/-</sup> mice do not develop Th1-type granulomas.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-01-06 02:20:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/808328"], "description"=>"<p>Real time PCR analysis of spleens (A) and livers (B) from infected WT mice measuring mRNA for IRF-5. All data is presented as the mean ± SEM combined from two independent experiments, n = 6 mice per group.</p>", "links"=>[], "tags"=>["upregulated", "t-cells"], "article_id"=>478694, "categories"=>["Immunology", "Medicine", "Physics"], "users"=>["Andrea Paun", "Rashmi Bankoti", "Trupti Joshi", "Paula M. Pitha", "Simona Stäger"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1001246.g006", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_IRF_5_is_upregulated_in_T_cells_during_L_donovani_infection_/478694", "title"=>"IRF-5 is upregulated in T-cells during <i>L. donovani</i> infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-01-06 02:24:54"}

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Relative Metric

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