Host Responses to Intestinal Microbial Antigens in Gluten-Sensitive Mice
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{"title"=>"Host responses to intestinal microbial antigens in gluten-sensitive mice", "type"=>"journal", "authors"=>[{"first_name"=>"Jane M.", "last_name"=>"Natividad", "scopus_author_id"=>"23470366600"}, {"first_name"=>"Xianxi", "last_name"=>"Huang", "scopus_author_id"=>"11640992700"}, {"first_name"=>"Emma", "last_name"=>"Slack", "scopus_author_id"=>"8644152200"}, {"first_name"=>"Jennifer", "last_name"=>"Jury", "scopus_author_id"=>"7004287397"}, {"first_name"=>"Yolanda", "last_name"=>"Sanz", "scopus_author_id"=>"7003409923"}, {"first_name"=>"Chella", "last_name"=>"David", "scopus_author_id"=>"36045444800"}, {"first_name"=>"Emmanuel", "last_name"=>"Denou", "scopus_author_id"=>"8217892600"}, {"first_name"=>"Pinchang", "last_name"=>"Yang", "scopus_author_id"=>"35279014900"}, {"first_name"=>"Joseph", "last_name"=>"Murray", "scopus_author_id"=>"7404760232"}, {"first_name"=>"Kathy D.", "last_name"=>"McCoy", "scopus_author_id"=>"55203183600"}, {"first_name"=>"Elena F.", "last_name"=>"Verdú", "scopus_author_id"=>"8109011300"}], "year"=>2009, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"68149094492", "doi"=>"10.1371/journal.pone.0006472", "pui"=>"355036466", "pmid"=>"19649259", "scopus"=>"2-s2.0-68149094492", "issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"1eee5658-a2e3-3503-8501-53353bf6dc7a", "abstract"=>"BACKGROUND AND AIMS: Excessive uptake of commensal bacterial antigens through a permeable intestinal barrier may influence host responses to specific antigen in a genetically predisposed host. The aim of this study was to investigate whether intestinal barrier dysfunction induced by indomethacin treatment affects the host response to intestinal microbiota in gluten-sensitized HLA-DQ8/HCD4 mice.\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: HLA-DQ8/HCD4 mice were sensitized with gluten, and gavaged with indomethacin plus gluten. Intestinal permeability was assessed by Ussing chamber; epithelial cell (EC) ultra-structure by electron microscopy; RNA expression of genes coding for junctional proteins by Q-real-time PCR; immune response by in-vitro antigen-specific T-cell proliferation and cytokine analysis by cytometric bead array; intestinal microbiota by fluorescence in situ hybridization and analysis of systemic antibodies against intestinal microbiota by surface staining of live bacteria with serum followed by FACS analysis. Indomethacin led to a more pronounced increase in intestinal permeability in gluten-sensitized mice. These changes were accompanied by severe EC damage, decreased E-cadherin RNA level, elevated IFN-gamma in splenocyte culture supernatant, and production of significant IgM antibody against intestinal microbiota.\\n\\nCONCLUSION: Indomethacin potentiates barrier dysfunction and EC injury induced by gluten, affects systemic IFN-gamma production and the host response to intestinal microbiota antigens in HLA-DQ8/HCD4 mice. The results suggest that environmental factors that alter the intestinal barrier may predispose individuals to an increased susceptibility to gluten through a bystander immune activation to intestinal microbiota.", "link"=>"http://www.mendeley.com/research/host-responses-intestinal-microbial-antigens-glutensensitive-mice", "reader_count"=>56, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>5, "Researcher"=>12, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>6, "Other"=>2, "Student > Master"=>8, "Student > Bachelor"=>7, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>5, "Researcher"=>12, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>6, "Other"=>2, "Student > Master"=>8, "Student > Bachelor"=>7, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>5, "Medicine and Dentistry"=>16, "Agricultural and Biological Sciences"=>22, "Neuroscience"=>1, "Business, Management and Accounting"=>1, "Chemistry"=>1, "Social Sciences"=>1, "Computer Science"=>1, "Immunology and Microbiology"=>6}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>16}, "Neuroscience"=>{"Neuroscience"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>6}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>22}, "Computer Science"=>{"Computer Science"=>1}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"Netherlands"=>1, "United States"=>2, "France"=>2, "Spain"=>1}, "group_count"=>2}

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  • {"files"=>["https://ndownloader.figshare.com/files/888751"], "description"=>"<p>Mitochondrial ultra-structure was assessed by electron microscopy. Indomethacin increased the fraction of disrupted mitochondria. Gluten sensitization plus indomethacin treatment further increased the proportion of altered mitochondria. Data represent the means±SEM of 6 mice/group. Reperesentative pictures from (A) Control mouse, arrow: normal mitochondria; (B) Gluten-sensitized mouse; (C) Indomethacin-treated mouse, arrowhead: mitochondria with disrupted cristae; (D) Indomethacin-treated plus gluten-sensitized mouse, arrowhead: mitochondria with disrupted cristae.</p>", "links"=>[], "tags"=>["mitochondrial"], "article_id"=>559201, "categories"=>["Physiology", "Medicine"], "users"=>["Jane M. Natividad", "Xianxi Huang", "Emma Slack", "Jennifer Jury", "Yolanda Sanz", "Chella David", "Emmanuel Denou", "Pinchang Yang", "Joseph Murray", "Kathy D. McCoy", "Elena F. Verdu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006472.g002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Evaluation_of_mitochondrial_disruption_/559201", "title"=>"Evaluation of mitochondrial disruption.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-07-31 02:33:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/889248"], "description"=>"<p>Expressions of (A) IL-12p70, (B) IFN-γ, (C) IL-10 were determined by CBA analysis. Culture supernatants from gluten-sensitized plus indomethacin (Indo) treated mice showed increased IFN- γ (*p<0.01 vs all groups). Cultured splenocytes from gluten-sensitized mice, with or without indomethacin showed a trend for increased IL-10 release after PT-gliadin stimulation (p = 0.09). Data represent the means±SEM of 6 mice/group.</p>", "links"=>[], "tags"=>["supernatant", "splenocyte", "cultures", "incubation", "pt-gliadin"], "article_id"=>559690, "categories"=>["Physiology", "Medicine"], "users"=>["Jane M. Natividad", "Xianxi Huang", "Emma Slack", "Jennifer Jury", "Yolanda Sanz", "Chella David", "Emmanuel Denou", "Pinchang Yang", "Joseph Murray", "Kathy D. McCoy", "Elena F. Verdu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006472.g006", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cytokines_in_supernatant_of_splenocyte_cultures_after_incubation_with_PT_gliadin_black_or_medium_white_/559690", "title"=>"Cytokines in supernatant of splenocyte cultures after incubation with PT-gliadin (black) or medium (white).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-07-31 02:41:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/889517"], "description"=>"<p>Serum from indomethacin and gluten treated mice showed significant positive serum antibodies against their aerobic and anaerobic intestinal microbiota. (A) Representative FACS histogram from each treatment gated on IgM<sup>+</sup> cells; (B) Proportion of IgM<sup>+</sup> aerobic bacterial cells for each treatment groups; (C) Proportion of IgM<sup>+</sup> anaerobic bacterial cells for each treatment groups. Data represent the means±SEM of 6 mice/group.</p>", "links"=>[], "tags"=>["antibodies"], "article_id"=>559965, "categories"=>["Physiology", "Medicine"], "users"=>["Jane M. Natividad", "Xianxi Huang", "Emma Slack", "Jennifer Jury", "Yolanda Sanz", "Chella David", "Emmanuel Denou", "Pinchang Yang", "Joseph Murray", "Kathy D. McCoy", "Elena F. Verdu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006472.g008", "stats"=>{"downloads"=>1, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Systemic_antibodies_against_commensals_/559965", "title"=>"Systemic antibodies against commensals.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-07-31 02:46:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/889377"], "description"=>"<p>Using 9 different oligonucleotide probes and fluorescent <i>in situ</i> hybridization (FISH), microbial profile was investigated in the distal jejunum of sensitized mice with and without indomethacin. The results indicate a significant perturbation in the proportions of microbiota investigated in all 3 treatment-groups when compared to non-sensitized controls, and remarkably in the gluten-sensitized plus indomethacin group. These differences achieve statistical significance in Bifidobacteria (*p = 0.04 vs controls, +p = 0.03 vs gluten) and Clostridium Leptum cluster (both *p = 0.02 vs controls and gluten sensitized, **p = 0.04 vs indomethacin) compared to gluten-sensitized alone. Data represent the means±SEM of 6 mice/group.</p>", "links"=>[], "tags"=>["physiology/gastroenterology and hepatology", "physiology/immune response", "gastroenterology and hepatology/small intestine"], "article_id"=>559825, "categories"=>["Physiology", "Medicine"], "users"=>["Jane M. Natividad", "Xianxi Huang", "Emma Slack", "Jennifer Jury", "Yolanda Sanz", "Chella David", "Emmanuel Denou", "Pinchang Yang", "Joseph Murray", "Kathy D. McCoy", "Elena F. Verdu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006472.g007", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Microbiota_composition_/559825", "title"=>"Microbiota composition.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-07-31 02:43:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/888994"], "description"=>"<p>Real-time QPCR experiments were performed on jejunum collected from all groups 24 hours after the last gluten challenge. Gluten-sensitized and indomethacin alone-treated mice showed a trend for decreased expression of E-cadherin relative to non-sensitized controls. Gluten-sensitized plus indomethacin-treated mice showed marked down-regulation of E-cadherin RNA level relative to non-sensitized controls. Data represent the means±SEM of 6 mice/group.</p>", "links"=>[], "tags"=>["E-cadherin"], "article_id"=>559446, "categories"=>["Physiology", "Medicine"], "users"=>["Jane M. Natividad", "Xianxi Huang", "Emma Slack", "Jennifer Jury", "Yolanda Sanz", "Chella David", "Emmanuel Denou", "Pinchang Yang", "Joseph Murray", "Kathy D. McCoy", "Elena F. Verdu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006472.g004", "stats"=>{"downloads"=>2, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_RNA_level_of_E_cadherin_relative_to_control_non_sensitized_/559446", "title"=>"RNA level of E-cadherin relative to control (non-sensitized).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-07-31 02:37:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/888873"], "description"=>"<p>Epithelial ultra-structure was assessed by electron microscopy. A significant proportion of altered TJ was observed in gluten-sensitized plus indomethacin-treated mice. Indomethacin alone also increased the proportion of altered TJ but to a lesser extent than indomethacin plus gluten. Gluten sensitization alone tended to increase the proportion of altered TJ but this did not achieve statistical significance (p = 0.09 vs non-sensitized controls). Data represent the means±SEM of 5 mice/group. Representative pictures of (A–B) a control mouse, arrow: tight junction (TJ) with preserved structure; (C) Gluten-sensitized mouse, arrow: TJ with preserved structure; (D) Indomethacin-treated mouse showing one altered TJ (arrowhead) and 2 junctions with normal struture (arrows); (E–G) Gluten plus indometacin treated mouse; (E) arrowhead: microvilli (mv) height reduction, arrow: apical epithelial cell destruction; (F) Altered TJ, arrow: mitochondria (m) with disrupted cristae; (G) Several altered TJs.</p>", "links"=>[], "tags"=>["epithelial"], "article_id"=>559322, "categories"=>["Physiology", "Medicine"], "users"=>["Jane M. Natividad", "Xianxi Huang", "Emma Slack", "Jennifer Jury", "Yolanda Sanz", "Chella David", "Emmanuel Denou", "Pinchang Yang", "Joseph Murray", "Kathy D. McCoy", "Elena F. Verdu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006472.g003", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Apical_epithelial_cell_structural_abnormalities_/559322", "title"=>"Apical epithelial cell structural abnormalities.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-07-31 02:35:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/888650"], "description"=>"<p>Ussing-chamber experiments were performed on jejunum from all four groups 24 hours after the last gluten challenge. (A) Gluten-sensitized mice treated with indomethacin showed a significant increase in tissue conductance. (B) HRP flux (transcellular permeability) increased significantly in all treatment groups compared to non-sensitized controls, however the highest values were observed in gluten plus indomethacin treated mice. Data represent the means±SEM of 10 mice/group.</p>", "links"=>[], "tags"=>["physiology/gastroenterology and hepatology", "physiology/immune response", "gastroenterology and hepatology/small intestine"], "article_id"=>559100, "categories"=>["Physiology", "Medicine"], "users"=>["Jane M. Natividad", "Xianxi Huang", "Emma Slack", "Jennifer Jury", "Yolanda Sanz", "Chella David", "Emmanuel Denou", "Pinchang Yang", "Joseph Murray", "Kathy D. McCoy", "Elena F. Verdu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006472.g001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Intestinal_barrier_measurements_/559100", "title"=>"Intestinal barrier measurements.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-07-31 02:31:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/889136"], "description"=>"<p>Proliferation was measured by <sup>3</sup>H-thymidine incorporation and expressed as stimulation index. Splenocytes from gluten-sensitized mice treated with or without indomethacin exhibited increased proliferation compared to non-sensitized controls. Data represent the means±SEM of 6 mice/group.</p>", "links"=>[], "tags"=>["proliferation", "incubation", "pt"], "article_id"=>559581, "categories"=>["Physiology", "Medicine"], "users"=>["Jane M. Natividad", "Xianxi Huang", "Emma Slack", "Jennifer Jury", "Yolanda Sanz", "Chella David", "Emmanuel Denou", "Pinchang Yang", "Joseph Murray", "Kathy D. McCoy", "Elena F. Verdu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006472.g005", "stats"=>{"downloads"=>1, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Splenocyte_proliferation_after_incubation_with_PT_gliadin_/559581", "title"=>"Splenocyte proliferation after incubation with PT gliadin.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-07-31 02:39:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/440595", "https://ndownloader.figshare.com/files/440611", "https://ndownloader.figshare.com/files/440619", "https://ndownloader.figshare.com/files/440631", "https://ndownloader.figshare.com/files/440640", "https://ndownloader.figshare.com/files/440656", "https://ndownloader.figshare.com/files/440668", "https://ndownloader.figshare.com/files/440675", "https://ndownloader.figshare.com/files/440689", "https://ndownloader.figshare.com/files/440695"], "description"=>"<div><h3>Background and Aims</h3><p>Excessive uptake of commensal bacterial antigens through a permeable intestinal barrier may influence host responses to specific antigen in a genetically predisposed host. The aim of this study was to investigate whether intestinal barrier dysfunction induced by indomethacin treatment affects the host response to intestinal microbiota in gluten-sensitized HLA-DQ8/HCD4 mice.</p><h3>Methodology/Principal Findings</h3><p>HLA-DQ8/HCD4 mice were sensitized with gluten, and gavaged with indomethacin plus gluten. Intestinal permeability was assessed by Ussing chamber; epithelial cell (EC) ultra-structure by electron microscopy; RNA expression of genes coding for junctional proteins by Q-real-time PCR; immune response by <em>in-vitro</em> antigen-specific T-cell proliferation and cytokine analysis by cytometric bead array; intestinal microbiota by fluorescence in situ hybridization and analysis of systemic antibodies against intestinal microbiota by surface staining of live bacteria with serum followed by FACS analysis. Indomethacin led to a more pronounced increase in intestinal permeability in gluten-sensitized mice. These changes were accompanied by severe EC damage, decreased E-cadherin RNA level, elevated IFN-γ in splenocyte culture supernatant, and production of significant IgM antibody against intestinal microbiota.</p><h3>Conclusion</h3><p>Indomethacin potentiates barrier dysfunction and EC injury induced by gluten, affects systemic IFN-γ production and the host response to intestinal microbiota antigens in HLA-DQ8/HCD4 mice. The results suggest that environmental factors that alter the intestinal barrier may predispose individuals to an increased susceptibility to gluten through a bystander immune activation to intestinal microbiota.</p></div>", "links"=>[], "tags"=>["responses", "intestinal", "microbial", "antigens", "gluten-sensitive", "mice"], "article_id"=>146858, "categories"=>["Physiology", "Medicine"], "users"=>["Jane M. Natividad", "Xianxi Huang", "Emma Slack", "Jennifer Jury", "Yolanda Sanz", "Chella David", "Emmanuel Denou", "Pinchang Yang", "Joseph Murray", "Kathy D. McCoy", "Elena F. Verdu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0006472.s001", "https://dx.doi.org/10.1371/journal.pone.0006472.s002", "https://dx.doi.org/10.1371/journal.pone.0006472.s003", "https://dx.doi.org/10.1371/journal.pone.0006472.s004", "https://dx.doi.org/10.1371/journal.pone.0006472.s005", "https://dx.doi.org/10.1371/journal.pone.0006472.s006", "https://dx.doi.org/10.1371/journal.pone.0006472.s007", "https://dx.doi.org/10.1371/journal.pone.0006472.s008", "https://dx.doi.org/10.1371/journal.pone.0006472.s009", "https://dx.doi.org/10.1371/journal.pone.0006472.s010"], "stats"=>{"downloads"=>7, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Host_Responses_to_Intestinal_Microbial_Antigens_in_Gluten_Sensitive_Mice/146858", "title"=>"Host Responses to Intestinal Microbial Antigens in Gluten-Sensitive Mice", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2009-07-31 01:54:18"}

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  • {"unique-ip"=>"6", "full-text"=>"3", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"9", "full-text"=>"15", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}

Relative Metric

{"start_date"=>"2009-01-01T00:00:00Z", "end_date"=>"2009-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[349, 614, 744, 851, 955, 1059, 1167, 1262, 1352, 1431, 1516, 1593, 1668, 1746, 1817, 1883, 1950, 2017, 2075, 2141, 2198, 2254, 2313, 2368, 2424, 2474, 2534, 2591, 2651, 2710, 2776, 2837, 2892, 2953, 3014, 3072, 3130, 3186, 3251, 3307, 3366, 3427, 3500, 3561, 3627, 3688, 3759, 3821, 3888, 3950, 4010, 4070, 4131, 4189, 4242, 4307, 4370, 4431, 4491, 4549, 4608]}, {"subject_area"=>"/Biology and life sciences/Anatomy and physiology", "average_usage"=>[320, 564, 690, 796, 901, 1003, 1105, 1196, 1286, 1367, 1453, 1523, 1601, 1673, 1743, 1807, 1879, 1931, 1993, 2053, 2108, 2165, 2218, 2273, 2327, 2375, 2432, 2492, 2539, 2590, 2639, 2694, 2742, 2807, 2861, 2918, 2977, 3032, 3086, 3145, 3204, 3260, 3326, 3378, 3438, 3496, 3558, 3626]}, {"subject_area"=>"/Medicine and health sciences/Immunology", "average_usage"=>[306, 552, 683, 801, 902, 1004, 1103, 1192, 1279, 1350, 1434, 1503, 1564, 1641, 1705, 1779, 1833, 1887, 1946, 2001, 2054, 2105, 2167, 2218, 2270, 2307, 2358, 2410, 2454, 2504, 2560, 2608, 2656, 2713, 2757, 2807, 2856, 2912, 2959, 3010, 3059, 3111, 3162, 3216, 3282, 3336, 3393, 3453, 3512, 3569, 3623, 3687, 3746, 3792, 3838, 3888, 3938, 3997, 4059, 4114, 4152]}]}
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