Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin

Nita H. Salzman, Dipankar Ghosh, Kenneth M. Huttner, Yvonne Paterson and Charles L. Bevins ()
Additional contact information
Nita H. Salzman: Medical College of Wisconsin
Dipankar Ghosh: The Cleveland Clinic Foundation
Kenneth M. Huttner: Massachusetts General Hospital, Harvard Medical School
Yvonne Paterson: University of Pennsylvania School of Medicine
Charles L. Bevins: The Cleveland Clinic Foundation

Nature, 2003, vol. 422, issue 6931, 522-526

Abstract: Abstract Genetically encoded antibiotic peptides are evolutionarily ancient and widespread effector molecules of immune defence1,2,3. Mammalian defensins, one subset of such peptides, have been implicated in the antimicrobial defence capacity of phagocytic leukocytes and various epithelial cells4, but direct evidence of the magnitude of their in vivo effects have not been clearly demonstrated. Paneth cells, specialized epithelia of the small intestinal crypt, secrete abundant α-defensins and other antimicrobial polypeptides5,6 including human defensin 5 (HD-5; also known as DEFA5)7,8,9. Although antibiotic activity of HD-5 has been demonstrated in vitro9,10, functional studies of HD-5 biology have been limited by the lack of in vivo models. To study the in vivo role of HD-5, we developed a transgenic mouse model using a 2.9-kilobase HD-5 minigene containing two HD-5 exons and 1.4 kilobases of 5′-flanking sequence. Here we show that HD-5 expression in these mice is specific to Paneth cells and reflects endogenous enteric defensin gene expression. The storage and processing of transgenic HD-5 also matches that observed in humans. HD-5 transgenic mice were markedly resistant to oral challenge with virulent Salmonella typhimurium. These findings provide support for a critical in vivo role of epithelial-derived defensins in mammalian host defence.

Date: 2003
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/nature01520 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:422:y:2003:i:6931:d:10.1038_nature01520

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature01520

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().