The Role of Peroxisome Proliferator-Activated Receptor γ in Immune Responses to Enteroaggregative Escherichia coli Infection
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{"title"=>"The Role of Peroxisome Proliferator-Activated Receptor γ in Immune Responses to Enteroaggregative Escherichia coli Infection", "type"=>"journal", "authors"=>[{"first_name"=>"Casandra W.", "last_name"=>"Philipson", "scopus_author_id"=>"55613529300"}, {"first_name"=>"Josep", "last_name"=>"Bassaganya-Riera", "scopus_author_id"=>"6603033549"}, {"first_name"=>"Monica", "last_name"=>"Viladomiu", "scopus_author_id"=>"42962600000"}, {"first_name"=>"Mireia", "last_name"=>"Pedragosa", "scopus_author_id"=>"55017879700"}, {"first_name"=>"Richard L.", "last_name"=>"Guerrant", "scopus_author_id"=>"7101799297"}, {"first_name"=>"James K.", "last_name"=>"Roche", "scopus_author_id"=>"7202267890"}, {"first_name"=>"Raquel", "last_name"=>"Hontecillas", "scopus_author_id"=>"6602639316"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84874565215", "pmid"=>"23469071", "sgr"=>"84874565215", "doi"=>"10.1371/journal.pone.0057812", "isbn"=>"10.1371/journal.pone.0057812", "issn"=>"19326203", "pui"=>"368451087"}, "id"=>"d02e4066-f1b0-3936-92a0-4a300aa06f01", "abstract"=>"BACKGROUND: Enteroaggregative Escherichia coli (EAEC) is recognized as an emerging cause of persistent diarrhea and enteric disease worldwide. Mucosal immunity towards EAEC infections is incompletely understood due in part to the lack of appropriate animal models. This study presents a new mouse model and investigates the role of peroxisome proliferator-activated receptor gamma (PPARγ) in the modulation of host responses to EAEC in nourished and malnourished mice.\\n\\nMETHODS/PRINCIPAL FINDINGS: Wild-type and T cell-specific PPARγ null C57BL/6 mice were fed protein-deficient diets at weaning and challenged with 5×10(9)cfu EAEC strain JM221 to measure colonic gene expression and immune responses to EAEC. Antigen-specific responses to E. coli antigens were measured in nourished and malnourished mice following infection and demonstrated the immunosuppressive effects of malnutrition at the cellular level. At the molecular level, both pharmacological blockade and deletion of PPARγ in T cells resulted in upregulation of TGF-β, IL-6, IL-17 and anti-microbial peptides, enhanced Th17 responses, fewer colonic lesions, faster clearance of EAEC, and improved recovery. The beneficial effects of PPARγ blockade on weight loss and EAEC clearance were abrogated by neutralizing IL-17 in vivo.\\n\\nCONCLUSIONS: Our studies provide in vivo evidence supporting the beneficial role of mucosal innate and effector T cell responses on EAEC burden and suggest pharmacological blockade of PPARγ as a novel therapeutic intervention for EAEC infection.", "link"=>"http://www.mendeley.com/research/role-peroxisome-proliferatoractivated-receptor-%CE%B3-immune-responses-enteroaggregative-escherichia-coli", "reader_count"=>10, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>1, "Student > Ph. D. Student"=>3, "Student > Master"=>2, "Student > Bachelor"=>3}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>1, "Student > Ph. D. Student"=>3, "Student > Master"=>2, "Student > Bachelor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>8}, "reader_count_by_subdiscipline"=>{"Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>8}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/975077"], "description"=>"<p>Growth retardation in infected wild type mice is expressed as percent growth from day 0 after challenge (A). Enteroaggregative <i>Escherichia coli</i> (EAEC) burden in the colon was assessed by quantitative real time RT-PCR using bacterial DNA isolated from feces of infected mice treated with 1 µM PPARγ antagonist GW9662 (n = 3), 50 µg anti-IL17 and 1 µM GW9662 combined (n = 3) or untreated (n = 3). Asterisks indicate values where differences are statistically significant (<i>p</i><0.05), NS signifies no significant difference, and bars are present to indicate significance between groups.</p>", "links"=>[], "tags"=>["il-17", "abrogates", "beneficial", "gw9662", "bacterial"], "article_id"=>642929, "categories"=>["Chemistry", "Microbiology", "Immunology"], "users"=>["Casandra W. Philipson", "Josep Bassaganya-Riera", "Monica Viladomiu", "Mireia Pedragosa", "Richard L. Guerrant", "James K. Roche", "Raquel Hontecillas"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0057812.g005", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Neutralization_of_IL_17_abrogates_the_beneficial_effects_of_GW9662_on_weight_loss_and_bacterial_burden_/642929", "title"=>"Neutralization of IL-17 abrogates the beneficial effects of GW9662 on weight loss and bacterial burden.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-01 15:56:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/975063"], "description"=>"<p>Growth retardation in wild type (A) and T cell specific PPARγ deficient mice (B) is expressed as percent growth from day 0 after challenge. Gene expression for IL-6 and TNF-α in colonic tissue of malnourished C57BL/6 and PPARγ CD4cre+ mice was analyzed using quantitative real-time RT-PCR on day 5 PI (C). Representative photomicrographs of colonic specimens of infected mice at 5 or 14 days PI in infected wild type mice (D,E,I,J), infected mice lacking PPARγ expression in T cells (F,G,K,L), and uninfected controls (H,M). The top panel corresponds to nourished mice whereas the bottom panel corresponds to malnourished mice. Original magnification 200×. Boxes and arrows are areas where an amplified image (400×) is provided to emphasize examples of leukocyte infiltration, mucosal thickening, goblet cell hyperplasia, and vasodilation. Mice per group: n = 8. Asterisks indicate values where differences are statistically significant (<i>p</i><0.05).</p>", "links"=>[], "tags"=>["beneficial", "deficiency", "cells", "enteroaggregative", "escherichia", "coli"], "article_id"=>642917, "categories"=>["Chemistry", "Microbiology", "Immunology"], "users"=>["Casandra W. Philipson", "Josep Bassaganya-Riera", "Monica Viladomiu", "Mireia Pedragosa", "Richard L. Guerrant", "James K. Roche", "Raquel Hontecillas"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0057812.g001", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Early_beneficial_effects_of_PPAR_947_deficiency_in_T_cells_during_enteroaggregative_Escherichia_coli_EAEC_challenge_/642917", "title"=>"Early beneficial effects of PPARγ deficiency in T cells during enteroaggregative Escherichia coli (EAEC) challenge.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-01 15:53:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/975084", "https://ndownloader.figshare.com/files/975086", "https://ndownloader.figshare.com/files/975088", "https://ndownloader.figshare.com/files/975090", "https://ndownloader.figshare.com/files/975095", "https://ndownloader.figshare.com/files/975096"], "description"=>"<div><p>Background</p><p>Enteroaggregative <i>Escherichia coli</i> (EAEC) is recognized as an emerging cause of persistent diarrhea and enteric disease worldwide. Mucosal immunity towards EAEC infections is incompletely understood due in part to the lack of appropriate animal models. This study presents a new mouse model and investigates the role of peroxisome proliferator-activated receptor gamma (PPARγ) in the modulation of host responses to EAEC in nourished and malnourished mice.</p> <p>Methods/Principal Findings</p><p>Wild-type and T cell-specific PPARγ null C57BL/6 mice were fed protein-deficient diets at weaning and challenged with 5×10<sup>9</sup>cfu EAEC strain JM221 to measure colonic gene expression and immune responses to EAEC. Antigen-specific responses to <i>E. coli</i> antigens were measured in nourished and malnourished mice following infection and demonstrated the immunosuppressive effects of malnutrition at the cellular level. At the molecular level, both pharmacological blockade and deletion of PPARγ in T cells resulted in upregulation of TGF-β, IL-6, IL-17 and anti-microbial peptides, enhanced Th17 responses, fewer colonic lesions, faster clearance of EAEC, and improved recovery. The beneficial effects of PPARγ blockade on weight loss and EAEC clearance were abrogated by neutralizing IL-17 <i>in vivo</i>.</p> <p>Conclusions</p><p>Our studies provide <i>in vivo</i> evidence supporting the beneficial role of mucosal innate and effector T cell responses on EAEC burden and suggest pharmacological blockade of PPARγ as a novel therapeutic intervention for EAEC infection.</p> </div>", "links"=>[], "tags"=>["peroxisome", "proliferator-activated", "receptor", "responses", "enteroaggregative", "infection"], "article_id"=>642936, "categories"=>["Chemistry", "Microbiology", "Immunology"], "users"=>["Casandra W. Philipson", "Josep Bassaganya-Riera", "Monica Viladomiu", "Mireia Pedragosa", "Richard L. Guerrant", "James K. Roche", "Raquel Hontecillas"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0057812.s001", "https://dx.doi.org/10.1371/journal.pone.0057812.s002", "https://dx.doi.org/10.1371/journal.pone.0057812.s003", "https://dx.doi.org/10.1371/journal.pone.0057812.s004", "https://dx.doi.org/10.1371/journal.pone.0057812.s005", "https://dx.doi.org/10.1371/journal.pone.0057812.s006"], "stats"=>{"downloads"=>6, "page_views"=>33, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/The_Role_of_Peroxisome_Proliferator_Activated_Receptor_in_Immune_Responses_to_Enteroaggregative_Escherichia_coli_Infection__/642936", "title"=>"The Role of Peroxisome Proliferator-Activated Receptor γ in Immune Responses to Enteroaggregative <em>Escherichia coli</em> Infection", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-03-01 15:57:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/975067"], "description"=>"<p>Antigen specific recall responses of spleenocytes from mice infected with EAEC were measured ex vivo using the lymphocyte blastogenesis test. EAEC JM221 whole cell and whole cell sonicate were used in parallel to two negative controls, <i>E. coli</i> HS and mutant EAEC Aff/I strains as well as one positive control, concanavalin A (ConA). Lymphocyte proliferation is expressed stimulation indexes which are calculated by dividing the counts per minute (CPM) of antigen-stimulated wells by the CPM of unstimulated wells (A). IL-17 expression was assessed in colonic lamina propria (B) and whole blood (C) CD4+ T cells by flow cytometry and in the colon by quantitative real time RT-PCR (D) 14 days PI. Mice per group: n = 10. Asterisks indicate values where differences are statistically significant (<i>p</i><0.05) while bars connect groups where comparisons are made.</p>", "links"=>[], "tags"=>["responses", "enteroaggregative", "escherichia", "coli", "peroxisome", "proliferator-activated", "receptor", "mice", "bacterial"], "article_id"=>642921, "categories"=>["Chemistry", "Microbiology", "Immunology"], "users"=>["Casandra W. Philipson", "Josep Bassaganya-Riera", "Monica Viladomiu", "Mireia Pedragosa", "Richard L. Guerrant", "James K. Roche", "Raquel Hontecillas"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0057812.g002", "stats"=>{"downloads"=>2, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Immune_responses_during_enteroaggregative_Escherichia_coli_EAEC_infection_in_peroxisome_proliferator_activated_receptor_947_PPAR_947_deficient_mice_associated_with_bacterial_clearance_/642921", "title"=>"Immune responses during enteroaggregative Escherichia coli (EAEC) infection in peroxisome proliferator-activated receptor γ (PPARγ)-deficient mice associated with bacterial clearance.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-01 15:54:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/975068"], "description"=>"<p>Gene expression data from colonic tissue of malnourished C57BL/6 mice was analyzed using quantitative real-time RT-PCR and reported as values normalized to β-actin. IL-6, IL-1β, MCP-1, CCL20, and CXCL1 were quantified at day 5PI (mice per group: n = 10) (A–E) while IL-6, TGF-β, and IL-17 were quantified 14 days PI (n = 10) (F–H). Asterisks indicate values where differences are statistically significant (<i>p</i><0.05) while bars connect groups where comparisons are made.</p>", "links"=>[], "tags"=>["suggests", "helper", "17", "mice", "peroxisome", "proliferator-activated", "receptor"], "article_id"=>642922, "categories"=>["Chemistry", "Microbiology", "Immunology"], "users"=>["Casandra W. Philipson", "Josep Bassaganya-Riera", "Monica Viladomiu", "Mireia Pedragosa", "Richard L. Guerrant", "James K. Roche", "Raquel Hontecillas"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0057812.g003", "stats"=>{"downloads"=>2, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gene_expression_suggests_a_T_helper_17_response_in_mice_when_peroxisome_proliferator_activated_receptor_947_PPAR_947_is_antagonized_/642922", "title"=>"Gene expression suggests a T helper 17 response in mice when peroxisome proliferator-activated receptor γ (PPARγ) is antagonized.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-01 15:54:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/975075"], "description"=>"<p>Enteroaggregative <i>Escherichia coli</i> (EAEC) burden in colon was assessed by quantitative real time RT-PCR using bacterial DNA isolated from feces of infected mice treated with PPARγ antagonist GW9662 (n = 9) or left untreated (n = 9). Data is presented as CFU/mg of tissue. S100A8 and S100A9 gene expression was analyzed in colonic tissue from C57BL/6 malnourished mice at day 5 days PI (n = 10) using quantitative real-time RT-PCR (B and C). S100 proteins are presented as values normalized to β-actin. Asterisks indicate values where differences are statistically significant (<i>p</i><0.05).</p>", "links"=>[], "tags"=>["blockade", "peroxisome", "proliferator-activated", "receptor", "antimicrobial", "bacterial"], "article_id"=>642927, "categories"=>["Chemistry", "Microbiology", "Immunology"], "users"=>["Casandra W. Philipson", "Josep Bassaganya-Riera", "Monica Viladomiu", "Mireia Pedragosa", "Richard L. Guerrant", "James K. Roche", "Raquel Hontecillas"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0057812.g004", "stats"=>{"downloads"=>2, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pharmacological_blockade_of_peroxisome_proliferator_activated_receptor_947_PPAR_947_associated_with_antimicrobial_response_and_bacterial_clearance_/642927", "title"=>"Pharmacological blockade of peroxisome proliferator-activated receptor γ (PPARγ) associated with antimicrobial response and bacterial clearance.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-01 15:55:42"}

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Relative Metric

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