A Novel Mouse Model of Schistosoma haematobium Egg-Induced Immunopathology
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{"title"=>"A novel mouse model of schistosoma haematobium egg-induced immunopathology", "type"=>"journal", "authors"=>[{"first_name"=>"Chi Ling", "last_name"=>"Fu", "scopus_author_id"=>"54079693400"}, {"first_name"=>"Justin I.", "last_name"=>"Odegaard", "scopus_author_id"=>"14023393400"}, {"first_name"=>"De'Broski R.", "last_name"=>"Herbert", "scopus_author_id"=>"7201705798"}, {"first_name"=>"Michael H.", "last_name"=>"Hsieh", "scopus_author_id"=>"8956430300"}], "year"=>2012, "source"=>"PLoS Pathogens", "identifiers"=>{"pmid"=>"22479181", "doi"=>"10.1371/journal.ppat.1002605", "sgr"=>"84861220198", "isbn"=>"1553-7374 (Electronic)\\r1553-7366 (Linking)", "scopus"=>"2-s2.0-84861220198", "issn"=>"15537366", "pui"=>"364837154"}, "id"=>"4ba174c2-2cf7-3e3d-9d2f-032e4e08a934", "abstract"=>"<title>Author Summary</title> <p>Urogenital schistosomiasis (infection with parasitic <italic>Schistosoma haematobium</italic> worms, the most common human-specific <italic>Schistosoma</italic> species globally) affects over 112 million people worldwide. <italic>S. haematobium</italic> worms primarily lay eggs in the bladder, upper urinary and genital tracts, and the host immune response to these eggs is considered to cause almost all associated disease in these organs. Resulting conditions include hematuria (bloody urine), urinary frequency, fibrosis (internal scarring) of the urinary tract, increased risk of bladder cancer, and enhanced susceptibility to contracting HIV. Approximately 150,000 people die annually from <italic>S. haematobium</italic>-induced obstructive kidney failure alone, making this species one of the deadliest worms worldwide. Despite the importance of <italic>S. haematobium</italic>, a lack of an experimentally manipulable model has contributed to the paucity of research focusing on this parasite. We have circumvented the barriers to natural <italic>S. haematobium</italic> oviposition in the mouse bladder by directly microinjecting parasite eggs into the bladder wall. This triggers inflammation, hematuria, urinary frequency, fibrosis, egg shedding, and epithelial changes that are similar to that seen in clinical <italic>S. haematobium</italic> infections. Our model may provide new opportunities to better understand the basic molecular and cellular immunology of urogenital schistosomiasis and thereby contribute to the development of new diagnostics and therapeutics.</p>", "link"=>"http://www.mendeley.com/research/novel-mouse-model-schistosoma-haematobium-egginduced-immunopathology", "reader_count"=>63, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>3, "Researcher"=>18, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>16, "Student > Postgraduate"=>2, "Student > Master"=>9, "Other"=>4, "Student > Bachelor"=>4, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>3, "Researcher"=>18, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>16, "Student > Postgraduate"=>2, "Student > Master"=>9, "Other"=>4, "Student > Bachelor"=>4, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>2, "Unspecified"=>5, "Environmental Science"=>2, "Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>26, "Medicine and Dentistry"=>18, "Neuroscience"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Chemistry"=>1, "Immunology and Microbiology"=>3}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>18}, "Neuroscience"=>{"Neuroscience"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>26}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>5}, "Environmental Science"=>{"Environmental Science"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"United States"=>1, "United Kingdom"=>1, "Australia"=>1, "Switzerland"=>1, "Portugal"=>1}, "group_count"=>4}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/339287", "https://ndownloader.figshare.com/files/339327", "https://ndownloader.figshare.com/files/339489", "https://ndownloader.figshare.com/files/339620"], "description"=>"<div><p><em>Schistosoma haematobium</em> is the etiologic agent for urogenital schistosomiasis, a major source of morbidity and mortality for more than 112 million people worldwide. Infection with <em>S. haematobium</em> results in a variety of immunopathologic sequelae caused by parasite oviposition within the urinary tract, which drives inflammation, hematuria, fibrosis, bladder dysfunction, and increased susceptibility to urothelial carcinoma. While humans readily develop urogenital schistosomiasis, the lack of an experimentally-tractable model has greatly impaired our understanding of the mechanisms that underlie this important disease. We have developed an improved mouse model of <em>S. haematobium</em> urinary tract infection that recapitulates several aspects of human urogenital schistosomiasis. Following microinjection of purified <em>S. haematobium</em> eggs into the bladder wall, mice consistently develop macrophage-rich granulomata that persist for at least 3 months and pass eggs in their urine. Importantly, egg-injected mice also develop urinary tract fibrosis, bladder dysfunction, and various urothelial changes morphologically reminiscent of human urogenital schistosomiasis. As expected, <em>S. haematobium</em> egg-induced immune responses in the immediate microenvironment, draining lymph nodes, and systemic circulation are associated with a Type 2-dominant inflammatory response, characterized by high levels of interleukin-4, eosinophils, and IgE. Taken together, our novel mouse model may help facilitate a better understanding of the unique pathophysiological mechanisms of epithelial dysfunction, tissue fibrosis, and oncogenesis associated with urogenital schistosomiasis.</p> </div>", "links"=>[], "tags"=>["egg-induced", "immunopathology"], "article_id"=>127084, "categories"=>["Cancer", "Immunology"], "users"=>["Chi-Ling Fu", "Michael Hsieh", "Justin I. Odegaard", "De'Broski R. Herbert"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1002605.s001", "https://dx.doi.org/10.1371/journal.ppat.1002605.s002", "https://dx.doi.org/10.1371/journal.ppat.1002605.s003", "https://dx.doi.org/10.1371/journal.ppat.1002605.s004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/A_Novel_Mouse_Model_of_Schistosoma_haematobium_Egg_Induced_Immunopathology/127084", "title"=>"A Novel Mouse Model of <em>Schistosoma haematobium</em> Egg-Induced Immunopathology", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-03-29 01:58:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/661001"], "description"=>"<p>Intramural injection of <i>S. haematobium</i> eggs results in rapid and localized injection site response followed by progressive expansion and consolidation over several weeks (serial micro-ultrasonography of a single representative animal, <b>A–D</b>; histology, <b>E–H</b>). Lymphoid follicles in <b>H</b> are marked with arrowheads. Scale bars for panels E, I, J, and L (lower right hand corner for each) are 100 microns long. Immunohistochemical characterization demonstrates central macrophage granuloma formation around injected eggs (arrows) with peripheral accumulation of other inflammatory cells (<b>I–K</b>, anti-CD68 brown). Epithelioid cells (activated macrophages) are indicated with arrowheads. Egg injection also induces early and sustained urothelial hyperplasia with reactive nuclear changes (<b>L–O</b>).</p>", "links"=>[], "tags"=>["injection", "eggs", "synchronous", "granuloma"], "article_id"=>331487, "categories"=>["Cancer", "Infectious Diseases", "Immunology"], "users"=>["Chi-Ling Fu", "Justin I. Odegaard", "De'Broski R. Herbert", "Michael H. Hsieh"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1002605.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Bladder_wall_injection_of_S_haematobium_eggs_results_in_synchronous_granuloma_formation_/331487", "title"=>"Bladder wall injection of <i>S. haematobium</i> eggs results in synchronous granuloma formation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-29 00:24:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/661183"], "description"=>"<p>Egg-injected bladders demonstrate histologically-apparent fibrosis within granulomata beginning at post-injection day 7 (<b>A</b>, Masson's trichrome stain, collagen stains blue). Later time points demonstrate increased collagen staining area and intensity (<b>B</b>). Total bladder soluble collagen content correlates with histologic evaluation (<b>C</b>). Egg-injected mice demonstrate increased urinary frequency (1 week post injection, <b>D</b>).</p>", "links"=>[], "tags"=>["egg-injected", "bladders", "fibrosis", "urinary"], "article_id"=>331671, "categories"=>["Cancer", "Infectious Diseases", "Immunology"], "users"=>["Chi-Ling Fu", "Justin I. Odegaard", "De'Broski R. Herbert", "Michael H. Hsieh"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1002605.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_S_haematobium_egg_injected_bladders_develop_fibrosis_and_urinary_dysfunction_/331671", "title"=>"<i>S. haematobium</i> egg-injected bladders develop fibrosis and urinary dysfunction.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-29 00:27:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/661287"], "description"=>"<p>Egg-injected bladders feature elevated levels of the Type 2-associated cytokines IL-4, IL-13, and eotaxin (<b>A</b>) without significant changes in T<sub>H</sub>1- or T<sub>H</sub>17-associated cytokines (e.g. IFN-γ [<b>B</b>] and IL-17 [<b>C</b>], respectively). Cytokines and chemokines associated with innate immune activation (e.g. KC, TNF-α, MIP-1α, MCP-3, [<b>D</b>]) are persistently elevated relative to control. The immunosuppressive cytokines IL-10 and TGF-β were not clearly differentially regulated in egg- versus control-injected mice (<b>E</b>).</p>", "links"=>[], "tags"=>["egg-injected", "bladders"], "article_id"=>331775, "categories"=>["Cancer", "Infectious Diseases", "Immunology"], "users"=>["Chi-Ling Fu", "Justin I. Odegaard", "De'Broski R. Herbert", "Michael H. Hsieh"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1002605.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_S_haematobium_egg_injected_bladders_demonstrate_a_local_Type_2_immune_response_/331775", "title"=>"<i>S. haematobium</i> egg-injected bladders demonstrate a local Type 2 immune response.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-29 00:29:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/661397"], "description"=>"<p>Congruent with histologic evaluation, serial flow cytometric analyses of single cell suspensions made from egg-injected bladders demonstrate progressive accumulation of (<b>A</b>) eosinophils (SiglecF<sup>+</sup>CCR3<sup>+</sup>), (<b>B</b>) neutrophils (CD11b<sup>+</sup>Gr-1<sup>+</sup>), (<b>C</b>) B cells (B220<sup>+</sup>), and—to a lesser extent— (<b>D</b>) T cells (CD3<sup>+</sup>).</p>", "links"=>[], "tags"=>["egg-injected", "bladders", "accumulate", "inflammatory", "infiltrate", "dominated", "eosinophils"], "article_id"=>331879, "categories"=>["Cancer", "Infectious Diseases", "Immunology"], "users"=>["Chi-Ling Fu", "Justin I. Odegaard", "De'Broski R. Herbert", "Michael H. Hsieh"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1002605.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_S_haematobium_egg_injected_bladders_accumulate_a_mixed_inflammatory_infiltrate_dominated_by_eosinophils_and_neutrophils_/331879", "title"=>"<i>S. haematobium</i> egg-injected bladders accumulate a mixed inflammatory infiltrate dominated by eosinophils and neutrophils.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-29 00:31:19"}
  • {"files"=>["https://ndownloader.figshare.com/files/661491"], "description"=>"<p>Pelvic lymph nodes from egg-injected mice demonstrate persistently elevated expression of Type 2-associated cytokines (e.g. IL-4) without corresponding increases in the T<sub>H</sub>1-associated cytokines IFN-γ and IL-12. The T<sub>Reg</sub>-associated marker FoxP3 is suppressed late in the experimental time course, while the immunosuppressive cytokines IL-10 and TGF-β remain unchanged. IL-17 was not detected (N.D.).</p>", "links"=>[], "tags"=>["egg-injected", "mice", "responses", "draining", "lymph"], "article_id"=>331979, "categories"=>["Cancer", "Infectious Diseases", "Immunology"], "users"=>["Chi-Ling Fu", "Justin I. Odegaard", "De'Broski R. Herbert", "Michael H. Hsieh"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1002605.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_S_haematobium_egg_injected_mice_demonstrate_Type_2_immune_responses_in_draining_lymph_nodes_/331979", "title"=>"<i>S. haematobium</i> egg-injected mice demonstrate Type 2 immune responses in draining lymph nodes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-29 00:32:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/661593"], "description"=>"<p>Egg-injected mice demonstrate elevated serum levels of Type 2-associated cytokines (e.g. IL-5) with decreased or unchanged serum levels of T<sub>H</sub>1- and T<sub>H</sub>17-associated cytokines (e.g. IFN-γ and IL-17, respectively, [<b>A</b>]). The Type 2 bias in systemic cytokine expression parallels increased IgE production (<b>B</b>).</p>", "links"=>[], "tags"=>["egg-injected", "mice", "systemic", "cytokine", "immunoglobulin"], "article_id"=>332080, "categories"=>["Cancer", "Infectious Diseases", "Immunology"], "users"=>["Chi-Ling Fu", "Justin I. Odegaard", "De'Broski R. Herbert", "Michael H. Hsieh"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1002605.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_S_haematobium_egg_injected_mice_display_systemic_Type_2_cytokine_and_immunoglobulin_responses_/332080", "title"=>"<i>S. haematobium</i> egg-injected mice display systemic Type 2 cytokine and immunoglobulin responses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-29 00:34:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/661676"], "description"=>"<p>Assayed proteins.</p>", "links"=>[], "tags"=>["immunology", "Infectious diseases", "urology"], "article_id"=>332165, "categories"=>["Cancer", "Infectious Diseases", "Immunology"], "users"=>["Chi-Ling Fu", "Justin I. Odegaard", "De'Broski R. Herbert", "Michael H. Hsieh"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1002605.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Assayed_proteins_/332165", "title"=>"Assayed proteins.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-03-29 00:36:05"}

PMC Usage Stats | Further Information

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Relative Metric

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