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Intestinal inflammation and increased intestinal permeability in Plasmodium chabaudi AS infected mice
Background: Gastrointestinal symptoms are commonly associated with acute Plasmodium spp infection. Malaria-associated enteritis may provide an opportunity for enteric pathogens to breach the intestinal mucosa, resulting in life-threatening systemic infections. Methods: To investigate whether intesti...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
F1000 Research Limited
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9647155/ https://www.ncbi.nlm.nih.gov/pubmed/36408291 http://dx.doi.org/10.12688/wellcomeopenres.17781.2 |
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author | Mooney, Jason P DonVito, Sophia M Lim, Rivka Keith, Marianne Pickles, Lia Maguire, Eleanor A Wagner-Gamble, Tara Oldfield, Thomas Bermejo Pariente, Ana Ehimiyein, Ajoke M Philbey, Adrian A Bottomley, Christian Riley, Eleanor M Thompson, Joanne |
author_facet | Mooney, Jason P DonVito, Sophia M Lim, Rivka Keith, Marianne Pickles, Lia Maguire, Eleanor A Wagner-Gamble, Tara Oldfield, Thomas Bermejo Pariente, Ana Ehimiyein, Ajoke M Philbey, Adrian A Bottomley, Christian Riley, Eleanor M Thompson, Joanne |
author_sort | Mooney, Jason P |
collection | PubMed |
description | Background: Gastrointestinal symptoms are commonly associated with acute Plasmodium spp infection. Malaria-associated enteritis may provide an opportunity for enteric pathogens to breach the intestinal mucosa, resulting in life-threatening systemic infections. Methods: To investigate whether intestinal pathology also occurs during infection with a murine model of mild and resolving malaria, C57BL/6J mice were inoculated with recently mosquito-transmitted Plasmodium chabaudi AS. At schizogony, intestinal tissues were collected for quantification and localisation of immune mediators and malaria parasites, by PCR and immunohistochemistry. Inflammatory proteins were measured in plasma and faeces and intestinal permeability was assessed by FITC-dextran translocation after oral administration. Results: Parasitaemia peaked at approx. 1.5% at day 9 and resolved by day 14, with mice experiencing significant and transient anaemia but no weight loss. Plasma IFNγ, TNFα and IL10 were significantly elevated during peak infection and quantitative RT-PCR of the intestine revealed a significant increase in transcripts for ifng and cxcl10. Histological analysis revealed parasites within blood vessels of both the submucosa and intestinal villi and evidence of mild crypt hyperplasia. In faeces, concentrations of the inflammatory marker lactoferrin were significantly raised on days 9 and 11 and FITC-dextran was detected in plasma on days 7 to 14. At day 11, plasma FITC-dextran concentration was significantly positively correlated with peripheral parasitemia and faecal lactoferrin concentration. Conclusions: In summary, using a relevant, attenuated model of malaria, we have found that acute infection is associated with intestinal inflammation and increased intestinal permeability. This model can now be used to explore the mechanisms of parasite-induced intestinal inflammation and to assess the impact of increased intestinal permeability on translocation of enteropathogens. |
format | Online Article Text |
id | pubmed-9647155 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | F1000 Research Limited |
record_format | MEDLINE/PubMed |
spelling | pubmed-96471552022-11-18 Intestinal inflammation and increased intestinal permeability in Plasmodium chabaudi AS infected mice Mooney, Jason P DonVito, Sophia M Lim, Rivka Keith, Marianne Pickles, Lia Maguire, Eleanor A Wagner-Gamble, Tara Oldfield, Thomas Bermejo Pariente, Ana Ehimiyein, Ajoke M Philbey, Adrian A Bottomley, Christian Riley, Eleanor M Thompson, Joanne Wellcome Open Res Research Article Background: Gastrointestinal symptoms are commonly associated with acute Plasmodium spp infection. Malaria-associated enteritis may provide an opportunity for enteric pathogens to breach the intestinal mucosa, resulting in life-threatening systemic infections. Methods: To investigate whether intestinal pathology also occurs during infection with a murine model of mild and resolving malaria, C57BL/6J mice were inoculated with recently mosquito-transmitted Plasmodium chabaudi AS. At schizogony, intestinal tissues were collected for quantification and localisation of immune mediators and malaria parasites, by PCR and immunohistochemistry. Inflammatory proteins were measured in plasma and faeces and intestinal permeability was assessed by FITC-dextran translocation after oral administration. Results: Parasitaemia peaked at approx. 1.5% at day 9 and resolved by day 14, with mice experiencing significant and transient anaemia but no weight loss. Plasma IFNγ, TNFα and IL10 were significantly elevated during peak infection and quantitative RT-PCR of the intestine revealed a significant increase in transcripts for ifng and cxcl10. Histological analysis revealed parasites within blood vessels of both the submucosa and intestinal villi and evidence of mild crypt hyperplasia. In faeces, concentrations of the inflammatory marker lactoferrin were significantly raised on days 9 and 11 and FITC-dextran was detected in plasma on days 7 to 14. At day 11, plasma FITC-dextran concentration was significantly positively correlated with peripheral parasitemia and faecal lactoferrin concentration. Conclusions: In summary, using a relevant, attenuated model of malaria, we have found that acute infection is associated with intestinal inflammation and increased intestinal permeability. This model can now be used to explore the mechanisms of parasite-induced intestinal inflammation and to assess the impact of increased intestinal permeability on translocation of enteropathogens. F1000 Research Limited 2022-10-05 /pmc/articles/PMC9647155/ /pubmed/36408291 http://dx.doi.org/10.12688/wellcomeopenres.17781.2 Text en Copyright: © 2022 Mooney JP et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Mooney, Jason P DonVito, Sophia M Lim, Rivka Keith, Marianne Pickles, Lia Maguire, Eleanor A Wagner-Gamble, Tara Oldfield, Thomas Bermejo Pariente, Ana Ehimiyein, Ajoke M Philbey, Adrian A Bottomley, Christian Riley, Eleanor M Thompson, Joanne Intestinal inflammation and increased intestinal permeability in Plasmodium chabaudi AS infected mice |
title | Intestinal inflammation and increased intestinal permeability in
Plasmodium chabaudi AS infected mice |
title_full | Intestinal inflammation and increased intestinal permeability in
Plasmodium chabaudi AS infected mice |
title_fullStr | Intestinal inflammation and increased intestinal permeability in
Plasmodium chabaudi AS infected mice |
title_full_unstemmed | Intestinal inflammation and increased intestinal permeability in
Plasmodium chabaudi AS infected mice |
title_short | Intestinal inflammation and increased intestinal permeability in
Plasmodium chabaudi AS infected mice |
title_sort | intestinal inflammation and increased intestinal permeability in
plasmodium chabaudi as infected mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9647155/ https://www.ncbi.nlm.nih.gov/pubmed/36408291 http://dx.doi.org/10.12688/wellcomeopenres.17781.2 |
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