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Peroral Low-Dose Toxoplasma gondii Infection of Human Microbiota-Associated Mice — A Subacute Ileitis Model to Unravel Pathogen–Host Interactions
Within 1 week following high-dose Toxoplasma gondii infection, mice develop lethal necrotizing ileitis. However, data from a subacute T. gondii-induced ileitis model are scarce. Therefore, mice harboring a human gut microbiota were perorally infected with one cyst of T. gondii. Within 9 days post-in...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Akadémiai Kiadó
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038537/ https://www.ncbi.nlm.nih.gov/pubmed/29997912 http://dx.doi.org/10.1556/1886.2018.00005 |
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author | Heimesaat, Markus M. Escher, Ulrike Grunau, Anne Fiebiger, Ulrike Bereswill, Stefan |
author_facet | Heimesaat, Markus M. Escher, Ulrike Grunau, Anne Fiebiger, Ulrike Bereswill, Stefan |
author_sort | Heimesaat, Markus M. |
collection | PubMed |
description | Within 1 week following high-dose Toxoplasma gondii infection, mice develop lethal necrotizing ileitis. However, data from a subacute T. gondii-induced ileitis model are scarce. Therefore, mice harboring a human gut microbiota were perorally infected with one cyst of T. gondii. Within 9 days post-infection, the intestinal microbiota composition shifted towards higher loads of commensal enterobacteria and enterococci. Following T. gondii infection, mice were clinically only mildly affected, whereas ≈60% of mice displayed fecal blood and mild-to-moderate ileal histopathological changes. Intestinal inflammation was further characterized by increased apoptotic intestinal epithelial cells, which were accompanied by elevated proliferating gut epithelial cell numbers. As compared to naive controls, infected mice displayed elevated numbers of intestinal T lymphocytes and regulatory T-cells and increased pro-inflammatory mediator secretion. Remarkably, T. gondii-induced apoptotic and pro-inflammatory immune responses were not restricted to the gut, but could also be observed in extra-intestinal compartments including kidney, liver, and lung. Strikingly, low-dose T. gondii infection resulted in increased serum levels of pro- and anti-inflammatory cytokines. In conclusion, the here presented subacute ileitis model following peroral low-dose T. gondii infection of humanized mice allows for detailed investigations of the molecular mechanism underlying the “ménage à trois” of pathogens, human gut microbiota, and immunity. |
format | Online Article Text |
id | pubmed-6038537 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Akadémiai Kiadó |
record_format | MEDLINE/PubMed |
spelling | pubmed-60385372018-07-11 Peroral Low-Dose Toxoplasma gondii Infection of Human Microbiota-Associated Mice — A Subacute Ileitis Model to Unravel Pathogen–Host Interactions Heimesaat, Markus M. Escher, Ulrike Grunau, Anne Fiebiger, Ulrike Bereswill, Stefan Eur J Microbiol Immunol (Bp) Original Research Paper Within 1 week following high-dose Toxoplasma gondii infection, mice develop lethal necrotizing ileitis. However, data from a subacute T. gondii-induced ileitis model are scarce. Therefore, mice harboring a human gut microbiota were perorally infected with one cyst of T. gondii. Within 9 days post-infection, the intestinal microbiota composition shifted towards higher loads of commensal enterobacteria and enterococci. Following T. gondii infection, mice were clinically only mildly affected, whereas ≈60% of mice displayed fecal blood and mild-to-moderate ileal histopathological changes. Intestinal inflammation was further characterized by increased apoptotic intestinal epithelial cells, which were accompanied by elevated proliferating gut epithelial cell numbers. As compared to naive controls, infected mice displayed elevated numbers of intestinal T lymphocytes and regulatory T-cells and increased pro-inflammatory mediator secretion. Remarkably, T. gondii-induced apoptotic and pro-inflammatory immune responses were not restricted to the gut, but could also be observed in extra-intestinal compartments including kidney, liver, and lung. Strikingly, low-dose T. gondii infection resulted in increased serum levels of pro- and anti-inflammatory cytokines. In conclusion, the here presented subacute ileitis model following peroral low-dose T. gondii infection of humanized mice allows for detailed investigations of the molecular mechanism underlying the “ménage à trois” of pathogens, human gut microbiota, and immunity. Akadémiai Kiadó 2018-04-16 /pmc/articles/PMC6038537/ /pubmed/29997912 http://dx.doi.org/10.1556/1886.2018.00005 Text en © 2018, The Author(s) http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and reproduction in any medium for non-commercial purposes, provided the original author and source are credited, a link to the CC License is provided, and changes – if any – are indicated. |
spellingShingle | Original Research Paper Heimesaat, Markus M. Escher, Ulrike Grunau, Anne Fiebiger, Ulrike Bereswill, Stefan Peroral Low-Dose Toxoplasma gondii Infection of Human Microbiota-Associated Mice — A Subacute Ileitis Model to Unravel Pathogen–Host Interactions |
title | Peroral Low-Dose Toxoplasma gondii Infection of Human Microbiota-Associated Mice — A Subacute Ileitis Model to Unravel Pathogen–Host Interactions |
title_full | Peroral Low-Dose Toxoplasma gondii Infection of Human Microbiota-Associated Mice — A Subacute Ileitis Model to Unravel Pathogen–Host Interactions |
title_fullStr | Peroral Low-Dose Toxoplasma gondii Infection of Human Microbiota-Associated Mice — A Subacute Ileitis Model to Unravel Pathogen–Host Interactions |
title_full_unstemmed | Peroral Low-Dose Toxoplasma gondii Infection of Human Microbiota-Associated Mice — A Subacute Ileitis Model to Unravel Pathogen–Host Interactions |
title_short | Peroral Low-Dose Toxoplasma gondii Infection of Human Microbiota-Associated Mice — A Subacute Ileitis Model to Unravel Pathogen–Host Interactions |
title_sort | peroral low-dose toxoplasma gondii infection of human microbiota-associated mice — a subacute ileitis model to unravel pathogen–host interactions |
topic | Original Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038537/ https://www.ncbi.nlm.nih.gov/pubmed/29997912 http://dx.doi.org/10.1556/1886.2018.00005 |
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