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Infection and Immunity, November 2009, p. 5163-5169, Vol. 77, No. 11
0019-9567/09/$08.00+0     doi:10.1128/IAI.00220-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Cryptosporidium parvum Isolate-Dependent Postinfectious Jejunal Hypersensitivity and Mast Cell Accumulation in an Immunocompetent Rat Model{triangledown}

Samira Khaldi,1,5 Gilles Gargala,1* Laetitia Le Goff,1 Simon Parey,2 Arnaud Francois,2 Jean Fioramonti,3 Jean-Jacques Ballet,4 Jean-Paul Dupont,5 Philippe Ducrotté,6 and Loïc Favennec1

Parasitology Laboratory, Rouen University Hospital, and ADEN EA 4311-IFRMP 23, Institute for Biomedical Research, University of Rouen, Rouen, France,1 Histopathology Laboratory, Rouen University Hospital and University of Rouen, Rouen, France,2 Neurogastroenterology and Nutrition Unit, INRA, Toulouse, France,3 Immunology Department, Caen University Hospital, and UPRES EA2128, University of Caen, Caen, France,4 M2C UMR CNRS 6143, University of Rouen, Rouen, France,5 Gastroenterology Unit, Rouen University Hospital, and ADEN EA 4311-IFRMP 23, Institute for Biomedical Research, University of Rouen, Rouen, France6

Received 25 February 2009/ Returned for modification 16 April 2009/ Accepted 10 August 2009

Cryptosporidium spp. are a cause of self-limited diarrhea in immunocompetent hosts. In immunocompetent rats, Cryptosporidium parvum infection induced digestive hypersensitivity, a key pathophysiological factor in functional digestive disorders such as irritable bowel syndrome (IBS). In such a rat model, we sought to document whether jejunal hypersensitivity depends on C. parvum isolate and is associated with a mast cell accumulation. Five-day-old rats were orally administered 105 oocysts of either Nouzilly (NoI) or Iowa (IoI) C. parvum isolate. NoI-infected rats exhibited the lowest food intake on days 7 and 14 postinfection (p.i.). On day 7 p.i., small intestine villus atrophy, crypt hyperplasia, and inflammatory cell infiltration were prominent in NoI-infected rats, with higher numbers of Cryptosporidium forms than in IoI-infected rats. Compared to uninfected control rats, jejunal intraepithelial lymphocytes (IELs) were increased only in NoI-infected rats on day 14 p.i. On day 50 p.i., jejunal hypersensitivity to distension was found only in NoI-infected rats; this hypersensitivity is associated with activated mast cell accumulation. The number of mast cells in the jejunal lamina propria was increased from day 36 p.i. in NoI-infected rats and only at day 120 p.i. in IoI-infected rats. Our data suggest that both the severity of infection (weight loss, reduced food intake, villus atrophy, and IEL accumulation) and the onset of a jejunal hypersensitivity after infection in association with an activated mast cell accumulation are isolate dependent and related to NoI infection. This cryptosporidiosis rat model is a relevant model for the study of underlying mechanisms of postinfectious IBS-like symptoms.


* Corresponding author. Mailing address: Laboratoire de Parasitologie-Mycologie, CHU Charles Nicolle, 1, Rue de Germont, 76031 Rouen Cedex, France. Phone: 33(0)2 32 88 01 15. Fax: 33(0)2 35 14 82 26. E-mail: gilles.gargala{at}univ-rouen.fr

{triangledown} Published ahead of print on 17 August 2009.

Editor: J. F. Urban, Jr.


Infection and Immunity, November 2009, p. 5163-5169, Vol. 77, No. 11
0019-9567/09/$08.00+0     doi:10.1128/IAI.00220-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.