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Mouse Paneth cell antimicrobial function is independent of Nod2.
- Source :
-
Gut [Gut] 2014 Jun; Vol. 63 (6), pp. 903-10. Date of Electronic Publication: 2013 Mar 19. - Publication Year :
- 2014
-
Abstract
- Objective: Although polymorphisms of the NOD2 gene predispose to the development of ileal Crohn's disease, the precise mechanisms of this increased susceptibility remain unclear. Previous work has shown that transcript expression of the Paneth cell (PC) antimicrobial peptides (AMPs) α-defensin 4 and α-defensin-related sequence 10 are selectively decreased in Nod2(-/-) mice. However, the specific mouse background used in this previous study is unclear. In light of recent evidence suggesting that mouse strain strongly influences PC antimicrobial activity, we sought to characterise PC AMP function in commercially available Nod2(-/-) mice on a C57BL/6 (B6) background. Specifically, we hypothesised that Nod2(-/-) B6 mice would display reduced AMP expression and activity.<br />Design: Wild-type (WT) and Nod2(-/-) B6 ileal AMP expression was assessed via real-time PCR, acid urea polyacrylamide gel electrophoresis and mass spectrometry. PCs were enumerated using flow cytometry. Functionally, α-defensin bactericidal activity was evaluated using a gel-overlay antimicrobial assay. Faecal microbial composition was determined using 454-sequencing of the bacterial 16S gene in cohoused WT and Nod2(-/-) littermates.<br />Results: WT and Nod2(-/-) B6 mice displayed similar PC AMP expression patterns, equivalent α-defensin profiles, and identical antimicrobial activity against commensal and pathogenic bacterial strains. Furthermore, minimal differences in gut microbial composition were detected between the two cohoused, littermate mouse groups.<br />Conclusions: Our data reveal that Nod2 does not directly regulate PC antimicrobial activity in B6 mice. Moreover, we demonstrate that previously reported Nod2-dependent influences on gut microbial composition may be overcome by environmental factors, such as cohousing with WT littermates.
- Subjects :
- Animals
Antigens, Neoplasm metabolism
Biomarkers, Tumor metabolism
Defensins genetics
Defensins metabolism
Escherichia coli drug effects
Ileum cytology
Lectins, C-Type metabolism
Mice, Inbred C57BL
Mice, Knockout
Microbial Sensitivity Tests
Muramidase metabolism
Nod2 Signaling Adaptor Protein genetics
Pancreatitis-Associated Proteins
Paneth Cells cytology
Peptides genetics
Peptides metabolism
Protein Precursors genetics
Protein Precursors metabolism
Ribonuclease, Pancreatic genetics
Ribonuclease, Pancreatic metabolism
Salmonella enterica drug effects
Transcription, Genetic
alpha-Defensins genetics
alpha-Defensins pharmacology
Feces microbiology
Ileum metabolism
Nod2 Signaling Adaptor Protein metabolism
Paneth Cells metabolism
RNA, Messenger metabolism
alpha-Defensins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1468-3288
- Volume :
- 63
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Gut
- Publication Type :
- Academic Journal
- Accession number :
- 23512834
- Full Text :
- https://doi.org/10.1136/gutjnl-2012-304190