title: Early phase morphological lesions and transcriptional responses of bovine ileum infected with Mycobacterium avium subsp. paratuberculosis.
abstract: Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of chronic enteritis in ruminants (Johne's disease) and a possible etiopathologic agent in human Crohn's disease. The host-pathogen interaction in this chronic disease has largely depended on the randomly collected static lesions studied in subclinically or clinically infected animals. We have established and utilized the neonatal calf ligated ileal loop model to study the early temporal host changes during MAP infection. After inoculation of ligated ileal loop with MAP, samples were analyzed for bacterial invasion, histologic and ultrastructural morphologic changes, and gene expression at several times (0.5-12 hours) postinfection. Our results indicate that MAP invades the intestinal mucosa as early as 0.5 hour postinoculation. Distribution and migration of neutrophils, monocytes/macrophages, and goblet cells were confirmed by histopathology, scanning and transmission electron microscopy. Coincident with the morphologic analysis, we measured by real-time polymerase chain reaction gene expression of various cytokines/chemokines that are involved in the recruitment of mononuclear and polymorphonuclear leukocytes to the site of infection. We also detected expression of several other genes, including intestinal-trefoil factor, profilin, lactoferrin, and enteric ss-defensin, which may play significant roles in the early MAP infection. Thus, the calf ligated intestinal loop model may be used as a human disease model to understand the role of MAP in the pathogenesis of Crohn's disease.
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Veterinary Research Building, Bldg. 1197, Room 141, Texas A&M University, College Station, TX 77843-4467, USA.
authors.forename: S
authors.initials: S
authors.lastname: Khare
authors.forename: J S
authors.initials: JS
authors.lastname: Nunes
authors.forename: J F
authors.initials: JF
authors.lastname: Figueiredo
authors.forename: S D
authors.initials: SD
authors.lastname: Lawhon
authors.forename: C A
authors.initials: CA
authors.lastname: Rossetti
authors.forename: T
authors.initials: T
authors.lastname: Gull
authors.forename: A C
authors.initials: AC
authors.lastname: Rice-Ficht
authors.forename: L G
authors.initials: LG
authors.lastname: Adams
mesh_terms: D000818:Animals; D002417:Cattle; D003424:Crohn Disease / Q000473:pathology*; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology; D007082:Ileum / Q000378:metabolism / Q000382:microbiology / Q000648:ultrastructure*; D008297:Male; D008854:Microscopy, Electron; D016927:Mycobacterium avium subsp. paratuberculosis; D010283:Paratuberculosis / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers