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A Novel Mouse Model of Schistosoma haematobium Egg-Induced Immunopathology

Schistosoma haematobium is the etiologic agent for urogenital schistosomiasis, a major source of morbidity and mortality for more than 112 million people worldwide. Infection with S. haematobium results in a variety of immunopathologic sequelae caused by parasite oviposition within the urinary tract...

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Autores principales: Fu, Chi-Ling, Odegaard, Justin I., Herbert, De'Broski R., Hsieh, Michael H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315496/
https://www.ncbi.nlm.nih.gov/pubmed/22479181
http://dx.doi.org/10.1371/journal.ppat.1002605
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author Fu, Chi-Ling
Odegaard, Justin I.
Herbert, De'Broski R.
Hsieh, Michael H.
author_facet Fu, Chi-Ling
Odegaard, Justin I.
Herbert, De'Broski R.
Hsieh, Michael H.
author_sort Fu, Chi-Ling
collection PubMed
description Schistosoma haematobium is the etiologic agent for urogenital schistosomiasis, a major source of morbidity and mortality for more than 112 million people worldwide. Infection with S. haematobium 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 S. haematobium urinary tract infection that recapitulates several aspects of human urogenital schistosomiasis. Following microinjection of purified S. haematobium 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, S. haematobium 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.
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spelling pubmed-33154962012-04-04 A Novel Mouse Model of Schistosoma haematobium Egg-Induced Immunopathology Fu, Chi-Ling Odegaard, Justin I. Herbert, De'Broski R. Hsieh, Michael H. PLoS Pathog Research Article Schistosoma haematobium is the etiologic agent for urogenital schistosomiasis, a major source of morbidity and mortality for more than 112 million people worldwide. Infection with S. haematobium 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 S. haematobium urinary tract infection that recapitulates several aspects of human urogenital schistosomiasis. Following microinjection of purified S. haematobium 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, S. haematobium 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. Public Library of Science 2012-03-29 /pmc/articles/PMC3315496/ /pubmed/22479181 http://dx.doi.org/10.1371/journal.ppat.1002605 Text en Fu et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Fu, Chi-Ling
Odegaard, Justin I.
Herbert, De'Broski R.
Hsieh, Michael H.
A Novel Mouse Model of Schistosoma haematobium Egg-Induced Immunopathology
title A Novel Mouse Model of Schistosoma haematobium Egg-Induced Immunopathology
title_full A Novel Mouse Model of Schistosoma haematobium Egg-Induced Immunopathology
title_fullStr A Novel Mouse Model of Schistosoma haematobium Egg-Induced Immunopathology
title_full_unstemmed A Novel Mouse Model of Schistosoma haematobium Egg-Induced Immunopathology
title_short A Novel Mouse Model of Schistosoma haematobium Egg-Induced Immunopathology
title_sort novel mouse model of schistosoma haematobium egg-induced immunopathology
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315496/
https://www.ncbi.nlm.nih.gov/pubmed/22479181
http://dx.doi.org/10.1371/journal.ppat.1002605
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