title: Cryptosporidium parvum isolate-dependent postinfectious jejunal hypersensitivity and mast cell accumulation in an immunocompetent rat model.
abstract: 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 10(5) 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.
authors.affiliation: Parasitology Laboratory, Rouen University Hospital, and Institute for Biomedical Research, University of Rouen, Rouen, France.
authors.forename: Samira
authors.initials: S
authors.lastname: Khaldi
authors.forename: Gilles
authors.initials: G
authors.lastname: Gargala
authors.forename: Laetitia
authors.initials: L
authors.lastname: Le Goff
authors.forename: Simon
authors.initials: S
authors.lastname: Parey
authors.forename: Arnaud
authors.initials: A
authors.lastname: Francois
authors.forename: Jean
authors.initials: J
authors.lastname: Fioramonti
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Ballet
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Dupont
authors.forename: Philippe
authors.initials: P
authors.lastname: Ducrotté
authors.forename: Loïc
authors.initials: L
authors.lastname: Favennec
mesh_terms: D000818:Animals; D003457:Cryptosporidiosis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D016785:Cryptosporidium parvum / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology; D007583:Jejunum / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D008407:Mast Cells / Q000276:immunology*; D017288:Pain Threshold; D051381:Rats
references.citation: Monogr Allergy. 1990;27:1-30
references.pmid: 2084533
references.citation: J Pharmacol Exp Ther. 2006 Dec;319(3):1104-11
references.pmid: 16988056
references.citation: Am J Vet Res. 1996 Nov;57(11):1586-8
references.pmid: 8915434
references.citation: Parasitology. 1998 Dec;117 ( Pt 6):525-31
references.pmid: 9881376
references.citation: Curr Treat Options Gastroenterol. 2001 Aug;4(4):287-291
references.pmid: 11469986
references.citation: Gut. 2007 Feb;56(2):203-9
references.pmid: 17005763
references.citation: Gut. 2004 Apr;53(4):501-6
references.pmid: 15016743
references.citation: Am J Med Sci. 2000 Nov;320(5):304-9
references.pmid: 11093682
references.citation: Clin Infect Dis. 2004 Aug 15;39(4):504-10
references.pmid: 15356813
references.citation: J Invest Dermatol. 1982 Mar;78(3):206-9
references.pmid: 6276474
references.citation: Neurogastroenterol Motil. 2007 Jan;19(1 Suppl):20-8
references.pmid: 17280583
references.citation: Parasitol Res. 2005 Jul;96(5):326-30
references.pmid: 15924222
references.citation: Parasitol Res. 2003 Mar;89(5):364-70
references.pmid: 12632148
references.citation: Gastroenterology. 2004 Mar;126(3):693-702
references.pmid: 14988823
references.citation: Microbes Infect. 2007 Apr;9(5):574-82
references.pmid: 17395519
references.citation: J Parasitol. 1999 Apr;85(2):234-9
references.pmid: 10219301
references.citation: Proc Natl Acad Sci U S A. 1978 Jun;75(6):2785-9
references.pmid: 351615
references.citation: Dig Dis Sci. 1993 Sep;38(9):1590-5
references.pmid: 8359068
references.citation: Infect Immun. 1997 Nov;65(11):4761-9
references.pmid: 9353062
references.citation: Contrib Microbiol. 2000;6:116-39
references.pmid: 10943510
references.citation: Int J Parasitol. 2007 Jan;37(1):11-20
references.pmid: 17070814
references.citation: Appl Environ Microbiol. 1999 Sep;65(9):3936-41
references.pmid: 10473398
references.citation: J Protozool. 1991 Nov-Dec;38(6):103S-104S
references.pmid: 1818125
references.citation: Neurogastroenterol Motil. 2007 Jan;19(1 Suppl):89-119
references.pmid: 17280587
references.citation: Infect Immun. 2007 Mar;75(3):1137-43
references.pmid: 17158891
references.citation: Dig Dis Sci. 1995 Aug;40(8):1607-13
references.pmid: 7648957
references.citation: Infect Immun. 1991 Feb;59(2):718-20
references.pmid: 1987087
references.citation: Neurogastroenterol Motil. 2007 Jan;19(1 Suppl):62-88
references.pmid: 17280586
references.citation: N Engl J Med. 2001 Jun 14;344(24):1846-50
references.pmid: 11407347
references.citation: Parasitol Res. 2009 Apr;104(5):985-91
references.pmid: 19043739
references.citation: Infect Immun. 2002 Apr;70(4):2090-9
references.pmid: 11895975
references.citation: Immunology. 1982 Jul;46(3):487-95
references.pmid: 7047382
references.citation: J Antimicrob Chemother. 2006 Feb;57(2):353-5
references.pmid: 16361328
references.citation: Gastroenterology. 1996 Dec;111(6):1516-23
references.pmid: 8942730
references.citation: J Eukaryot Microbiol. 1997 Nov-Dec;44(6):71S-72S
references.pmid: 9508452
references.citation: Parasitol Res. 2001 Nov;87(11):891-6
references.pmid: 11728011
references.citation: N Engl J Med. 1995 Mar 30;332(13):855-9
references.pmid: 7870140
references.citation: J Gastroenterol Hepatol. 2006 Jan;21(1 Pt 1):71-8
references.pmid: 16706815
references.citation: Curr Opin Gastroenterol. 2006 Jan;22(1):13-7
references.pmid: 16319671
references.citation: Neurogastroenterol Motil. 2005 Dec;17(6):863-70
references.pmid: 16336502
references.citation: Clin Infect Dis. 2008 Feb 15;46(4):594-9
references.pmid: 18205536
references.citation: Gut. 1973 Feb;14(2):125-32
references.pmid: 4696535
references.citation: Infect Immun. 2006 Jul;74(7):4387-9
references.pmid: 16790818
references.citation: Neurogastroenterol Motil. 2004 Jun;16(3):311-4
references.pmid: 15198653
references.citation: N Engl J Med. 2004 Jan 1;350(1):38-47
references.pmid: 14702426
references.citation: Gastroenterology. 2007 Jan;132(1):26-37
references.pmid: 17241857
references.citation: Gastroenterology. 1990 May;98(5 Pt 1):1129-40
references.pmid: 2323506
references.citation: Parasitol Res. 2008 Nov;103(6):1289-95
references.pmid: 18677623
references.citation: J Parasitol. 2008 Oct;94(5):1150-4
references.pmid: 18576802
references.citation: Exp Parasitol. 1999 Feb;91(2):119-25
references.pmid: 9990339
references.citation: J Infect Dis. 1996 Jul;174(1):229-32
references.pmid: 8656002
references.citation: Gut. 2004 Aug;53(8):1096-101
references.pmid: 15247174
references.citation: Int J Parasitol. 2008 Jul;38(8-9):1051-5
references.pmid: 18096164
references.citation: J Vet Intern Med. 2002 Jan-Feb;16(1):12-21
references.pmid: 11822801
references.citation: Neurogastroenterol Motil. 1998 Dec;10(6):499-508
references.pmid: 10050255
references.citation: J Infect Dis. 1991 Jun;163(6):1297-304
references.pmid: 2037795
references.citation: J Infect Dis. 1999 Oct;180(4):1275-81
references.pmid: 10479158
references.citation: Parasitol Res. 2003 Oct;91(3):197-203
references.pmid: 12923633
references.citation: Infect Immun. 1992 Aug;60(8):3325-31
references.pmid: 1639500
references.citation: J Immunol. 1996 Jan 1;156(1):263-8
references.pmid: 8598471
references.citation: Eur J Pharmacol. 1997 Oct 22;337(2-3):279-82
references.pmid: 9430426
references.citation: Am J Physiol. 1992 Nov;263(5 Pt 1):G673-7
references.pmid: 1443141