title: Villus epithelial injury induced by infection with the nematode Nippostrongylus brasiliensis is associated with upregulation of granzyme B.
abstract: Intestinal parasite infections induce thymus-dependent villus atrophy, but the effector mechanisms directly responsible for the development of villus atrophy are not thoroughly understood. In this study, we analyzed the expression of cytotoxic factors or ligands in athymic nude rnu/rnu rats and their littermate euthymic rnu/+ rats infected with the nematode Nippostrongylus brasiliensis. Morphometric analyses showed that partial villus atrophy developed 10 days after infection in euthymic but not in athymic rats, whereas crypt hyperplasia occurred in both types of animal. Reverse transcription-polymerase chain reaction analyses of the isolated jejunal epithelial fraction showed that the development of villus atrophy in euthymic rats was positively correlated with an increase of granzyme B transcript levels but not with Fas ligand or tumor necrosis factor-alpha expression. In addition, the number of granzyme B-immunoreactive cells was increased significantly in euthymic rat villus epithelium and the propria mucosa after infection. The CD8+ cell number did not change significantly. Collectively, these findings showed that significant increases in the number of cells that express the cytotoxic factor granzyme B occur in the nematode-infected small intestine of immunocompetent hosts. The type of cells that express granzyme B and their role in the progression of enteropathy remain to be elucidated.
authors.affiliation: Department of Medical Zoology, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kyoto 602-8566, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fujiwara
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kawai
authors.forename: Shuji
authors.initials: S
authors.lastname: Sekikawa
authors.forename: Takahiro
authors.initials: T
authors.lastname: Horii
authors.forename: Minoru
authors.initials: M
authors.lastname: Yamada
authors.forename: Shoji
authors.initials: S
authors.lastname: Mitsufuji
authors.forename: Naoki
authors.initials: N
authors.lastname: Arizono
mesh_terms: D000818:Animals; D053222:Fas Ligand Protein; D005260:Female; D053804:Granzymes; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000469:parasitology / Q000473:pathology*; D007583:Jejunum / Q000469:parasitology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism; D008871:Microvilli / Q000469:parasitology / Q000473:pathology; D009559:Nippostrongylus / Q000201:enzymology* / Q000276:immunology / Q000472:pathogenicity; D051381:Rats; D011916:Rats, Inbred F344; D011923:Rats, Nude; D012697:Serine Endopeptidases / Q000378:metabolism*; D013047:Specific Pathogen-Free Organisms; D017206:Strongylida Infections / Q000201:enzymology / Q000276:immunology / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D053804:Granzymes; C509215:Gzmb protein, rat; D012697:Serine Endopeptidases