Intestinal inflammation and increased intestinal permeability in Plasmodium chabaudi AS infected mice [version 2; peer review: 2 approved]
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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wellcome
2022-10-01
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| Series: | Wellcome Open Research |
| Subjects: | |
| Online Access: | https://wellcomeopenresearch.org/articles/7-134/v2 |
| _version_ | 1828200064176095232 |
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| author | Jason P Mooney Christian Bottomley Rivka Lim Sophia M DonVito Lia Pickles Marianne Keith Tara Wagner-Gamble Eleanor A Maguire Ana Bermejo Pariente Thomas Oldfield Adrian A Philbey Ajoke M Ehimiyien Eleanor M Riley Joanne Thompson |
| author_facet | Jason P Mooney Christian Bottomley Rivka Lim Sophia M DonVito Lia Pickles Marianne Keith Tara Wagner-Gamble Eleanor A Maguire Ana Bermejo Pariente Thomas Oldfield Adrian A Philbey Ajoke M Ehimiyien Eleanor M Riley Joanne Thompson |
| author_sort | Jason P Mooney |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T11:07:27Z |
| format | Article |
| id | doaj.art-fc2331797d1640d395fdfd850c6a3a8d |
| institution | Directory Open Access Journal |
| issn | 2398-502X |
| language | English |
| last_indexed | 2024-04-12T11:07:27Z |
| publishDate | 2022-10-01 |
| publisher | Wellcome |
| record_format | Article |
| series | Wellcome Open Research |
| spelling | doaj.art-fc2331797d1640d395fdfd850c6a3a8d2022-12-22T03:35:44ZengWellcomeWellcome Open Research2398-502X2022-10-01720398Intestinal inflammation and increased intestinal permeability in Plasmodium chabaudi AS infected mice [version 2; peer review: 2 approved]Jason P Mooney0https://orcid.org/0000-0002-2824-124XChristian Bottomley1Rivka Lim2https://orcid.org/0000-0001-5247-7028Sophia M DonVito3https://orcid.org/0000-0001-8900-307XLia Pickles4Marianne Keith5Tara Wagner-Gamble6https://orcid.org/0000-0003-3608-2880Eleanor A Maguire7https://orcid.org/0000-0003-3459-1729Ana Bermejo Pariente8Thomas Oldfield9Adrian A Philbey10Ajoke M Ehimiyien11https://orcid.org/0000-0002-7505-6987Eleanor M Riley12Joanne Thompson13https://orcid.org/0000-0002-3343-2278Institute of Immunology and Infection Research, University of Ediburgh, Edinburgh, Midlothian, EH93JT, UKDepartment of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UKInstitute of Immunology and Infection Research, University of Ediburgh, Edinburgh, Midlothian, EH93JT, UKInstitute of Immunology and Infection Research, University of Ediburgh, Edinburgh, Midlothian, EH93JT, UKInstitute of Immunology and Infection Research, University of Ediburgh, Edinburgh, Midlothian, EH93JT, UKDivision of Infection and Immunity, The Roslin Institute, University of Edinburgh, Edinburgh, EH25 9RG, UKInstitute of Immunology and Infection Research, University of Ediburgh, Edinburgh, Midlothian, EH93JT, UKInstitute of Immunology and Infection Research, University of Ediburgh, Edinburgh, Midlothian, EH93JT, UKInstitute of Immunology and Infection Research, University of Ediburgh, Edinburgh, Midlothian, EH93JT, UKInstitute of Immunology and Infection Research, University of Ediburgh, Edinburgh, Midlothian, EH93JT, UKEaster Bush Pathology, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, United Kingdom., Edinburgh, EH25 9RG, UKInstitute of Immunology and Infection Research, University of Ediburgh, Edinburgh, Midlothian, EH93JT, UKInstitute of Immunology and Infection Research, University of Ediburgh, Edinburgh, Midlothian, EH93JT, UKInstitute of Immunology and Infection Research, University of Ediburgh, Edinburgh, Midlothian, EH93JT, UKBackground: 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.https://wellcomeopenresearch.org/articles/7-134/v2malaria plasmodium intestine permeability enteritiseng |
| spellingShingle | Jason P Mooney Christian Bottomley Rivka Lim Sophia M DonVito Lia Pickles Marianne Keith Tara Wagner-Gamble Eleanor A Maguire Ana Bermejo Pariente Thomas Oldfield Adrian A Philbey Ajoke M Ehimiyien Eleanor M Riley Joanne Thompson Intestinal inflammation and increased intestinal permeability in Plasmodium chabaudi AS infected mice [version 2; peer review: 2 approved] Wellcome Open Research malaria plasmodium intestine permeability enteritis eng |
| title | Intestinal inflammation and increased intestinal permeability in Plasmodium chabaudi AS infected mice [version 2; peer review: 2 approved] |
| title_full | Intestinal inflammation and increased intestinal permeability in Plasmodium chabaudi AS infected mice [version 2; peer review: 2 approved] |
| title_fullStr | Intestinal inflammation and increased intestinal permeability in Plasmodium chabaudi AS infected mice [version 2; peer review: 2 approved] |
| title_full_unstemmed | Intestinal inflammation and increased intestinal permeability in Plasmodium chabaudi AS infected mice [version 2; peer review: 2 approved] |
| title_short | Intestinal inflammation and increased intestinal permeability in Plasmodium chabaudi AS infected mice [version 2; peer review: 2 approved] |
| title_sort | intestinal inflammation and increased intestinal permeability in plasmodium chabaudi as infected mice version 2 peer review 2 approved |
| topic | malaria plasmodium intestine permeability enteritis eng |
| url | https://wellcomeopenresearch.org/articles/7-134/v2 |
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