Enhanced Host Immune Recognition of Mastitis Causing Escherchia Coli in CD-14 Transgenic Mice

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Abstract:

Escherchia coli causes mastitis, an economically significant disease in dairy animals. E. coli endotoxin (lipopolysaccharide, LPS) when bound by host membrane proteins such as CD-14, causes release of proinflammatory cytokines recruiting neutrophils as an early, innate immune response. Excessive proinflammatory cytokines causes tissue damage, compromising mammary function. If present, soluble CD-14 (sCD-14) might out compete membrane bound CD-14, lessening the severity of the inflammatory response. To test this hypothesis transgenic mice, expressing sCD-14 in their milk (31 to 316 g/ml), were evaluated. A cell culture study demonstrated, in the presence of LPS, milk from transgenic mice increased secretion of cytokine IL-8 compared to milk from nontransgenic littermates (18 ± 3 vs. 35 ± 2 ng/mL, p < 0.001). To assess protection afforded by the transgene, glands were infused with E. coli. Recovery of bacteria showed no clear relationship between sCD14 concentration and the number of organisms recovered; however, there was a strong relationship between sCD14 concentration and edema (r2 = 0.999, p < 0.001), as measured by weight of fluid in harvested glands. Highest expressing lines had the least edema, suggesting the presence of sCD14 had an effect on reducing the inflammatory response to E. coli, thus, possibly protecting against gland tissue damage.

Keywords: CD-14; Mammary gland; Mastitis; Transgenic mice

Document Type: Research Article

DOI: http://dx.doi.org/10.1080/10495390802594206

Affiliations: 1: Animal Bioscience and Biotechnology Laboratory, Agricultural Research Service, Beltsville, Maryland, USA 2: Genetic Disease Resistance Section, NIDDK, National Institutes of Health, Bethesda, Maryland, USA 3: Bovine Functional Genomics Laboratory, Agricultural Research Service, Beltsville, Maryland, USA

Publication date: January 1, 2009

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