Article

Early Phase Morphological Lesions and Transcriptional Responses of Bovine Ileum Infected with Mycobacterium avium subsp paratuberculosis

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.
Veterinary Pathology (Impact Factor: 2.04). 04/2009; 46(4):717-28. DOI: 10.1354/vp.08-VP-0187-G-FL
Source: PubMed

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.

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    • "This early stage infection process takes only a few hours (Clarke, 1997; Khare et al., 2009; Valentin-Weigand and Goethe, 1999). Upon maturation, phagosomes fuse with lysosomes and the mycobacteria undergo digestion by a process of acidification and enzymatic proteolysis. "
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    ABSTRACT: Evasion of host defense mechanisms and survival inside infected host macrophages are features of pathogenic mycobacteria including Mycobacterium avium subspecies paratuberculosis, the causative agent of Johne's disease in ruminants. Protein tyrosine phosphatase A (PtpA) has been identified as a secreted protein critical for survival of mycobacteria within infected macrophages. The host may mount an immune response to such secreted proteins. In this study, the humoral immune response to purified recombinant Mycobacterium avium subsp. paratuberculosis PtpA was investigated using sera from a cohort of sheep infected with Mycobacterium avium subsp. paratuberculosis and compared with uninfected healthy controls. A significantly higher level of reactivity to PtpA was observed in sera collected from Mycobacterium avium subspecies paratuberculosis infected sheep when compared to those from uninfected healthy controls. PtpA could be a potential candidate antigen for detection of humoral immune responses in sheep infected with Mycobacterium avium subspecies paratuberculosis.
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    • "Although intra-uterine transmission of MAP occurs (Sweeney et al., 1992a,b), MAP is typically acquired orally and most frequently in young calves (Whittington and Sergeant, 2001). From the intestinal lumen, MAP enters the host intestine through M cells, epithelial cells, antigen presenting cells and goblet cells of Peyer's patches in the ileum and jejunum (Khare et al., 2009; Momotani et al., 1988). Furthermore, MAP is phagocytized by macrophages located in the submucosal layers via receptor-mediated endocytosis (Zurbrick and Czuprynski, 1987). "
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