Molecular pathogenesis of Salmonella-induced enteritis in calves /
Salmonella enterica serotype Typhimurium (S. typhimurium) causes an enteric disease in cattle and man and is an important cause of food-borne infections. Here we demonstrated that macrophages infected with S. typhimurium grown in the logarithmic phase quickly underwent cell death, whereas stationary...
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| Format: | Thesis Book |
| Language: | English |
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[Place of publication not identified] :
[publisher not identified] ;
2001.
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| Online Access: | http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=726103341&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD |
| Summary: | Salmonella enterica serotype Typhimurium (S. typhimurium) causes an enteric disease in cattle and man and is an important cause of food-borne infections. Here we demonstrated that macrophages infected with S. typhimurium grown in the logarithmic phase quickly underwent cell death, whereas stationary cultures or a sipB mutant caused no immediate cell death but caused delayed cytotoxicity. Both pathways were inhibited by the caspase inhibitor Z-VAD-Fmk and by the caspase-1 inhibitor Z-YVAD-Fmk. The role of the Salmonella-induced cell death was investigated in vivo using ileal loops. Inflammation was detected in all infected loops at 1 hour post-infection, while fluid accumulation began at 3 hours post-infection. The level of cell death in wild type infected loops was significantly higher than the controls at 12 hours post-infection, when severe inflammation had already developed. The sopB mutant was able to cause cell death in spite of its attenuation for eliciting inflammation. Histologic and ultrastructural lesions as well as the profile of chemokine/cytokine expression were also investigated. Invasion of both M cells and enterocytes began at 15 minutes post-infection. A severe acute neutrophilic response was associated with invasion of the Peyer's patches. Increased expression of IL-8, GROα and γ, and GCP2 was detected beginning at 1 hour post-infection. A marked increase in expression of IL-1β was observed whereas expression of IL-18 and TNFα did not change after infection. Up-regulation of IL-1Ra and IL-4, but not IL-10, was observed. The host response to infection was further characterized by mRNA differential display, which resulted in identification of a cDNA highly homologous to a human plasma membrane calcium transporting ATPase (PMCA) that was down-regulated in bovine Peyer's patches after infection. In conclusion, S. typhimurium induces cell death in bovine macrophages by a potentially pro-inflammatory mechanism that is not required for early inflammatory responses in vivo. The host response to S. typhimurium, characterized by a massive recruitment of neutrophils, involves increased expression of pro-inflammatory mediators and is associated with down-regulation of PMCA in the Peyer's patches, which is thought to enhance recruitment of neutrophils and inflammation by favoring secretion of pro-inflammatory mediators by intestinal epithelial cells. |
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| Item Description: | Vita. "Major Subject: Veterinary Pathology". |
| Physical Description: | xiv, 196 leaves : illustrations ; 28 cm. Issued also on microfiche from University Microfilm Inc. |
| Bibliography: | Includes bibliographical references (leaves 151-195). |