Intestinal inflammation and increased intestinal permeability in Plasmodium chabaudi AS infected mice

Wellcome Open Research

article

Jason P Mooney¹  Sophia M DonVito¹  Rivka Lim¹  Marianne Keith²  Lia Pickles¹  Eleanor A Maguire¹  Tara Wagner-Gamble¹  Thomas Oldfield¹  Ana Bermejo Pariente¹  Ajoke M Ehimiyein¹  Adrian A Philbey⁵  Christian Bottomley⁶  Eleanor M Riley¹  Joanne Thompson¹ 

[1] Institute of Immunology and Infection Research, University of Ediburgh;Division of Infection and Immunity, The Roslin Institute, University of Edinburgh;Editorial Team, F1000 Ltd.;Department of Veterinary Medicine, Ahmadu Bello University;Easter Bush Pathology, Royal ,(Dick) School of Veterinary Studies, University of Edinburgh;Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine

关键词: malaria;    plasmodium;    intestine;    permeability;    enteritis;   

DOI  :  10.12688/wellcomeopenres.17781.2

学科分类：内科医学

来源: Wellcome

【 摘 要 】

Background: Gastrointestinal symptoms are commonly associated with acutePlasmodiumspp 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-transmittedPlasmodium 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 forifng andcxcl10. 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.

【 授权许可】

CC BY