Abstract
Antimicrobial peptides are important effectors of innate immunity throughout the plant and animal kingdoms. In the mammalian small intestine, Paneth cell alpha-defensins are antimicrobial peptides that contribute to host defense against enteric pathogens. To determine if alpha-defensins also govern intestinal microbial ecology, we analyzed the intestinal microbiota of mice expressing a human alpha-defensin gene (DEFA5) and in mice lacking an enzyme required for the processing of mouse alpha-defensins. In these complementary models, we detected significant alpha-defensin-dependent changes in microbiota composition, but not in total bacterial numbers. Furthermore, DEFA5-expressing mice had striking losses of segmented filamentous bacteria and fewer interleukin 17 (IL-17)-producing lamina propria T cells. Our data ascribe a new homeostatic role to alpha-defensins in regulating the makeup of the commensal microbiota.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bacteria / classification
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Bacteria / genetics
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Bacteria / growth & development
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Colony Count, Microbial
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Ecology*
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Female
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Flow Cytometry
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Humans
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In Situ Hybridization, Fluorescence
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Interleukin-17 / immunology
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Interleukin-17 / metabolism
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Intestinal Mucosa / metabolism*
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Intestine, Small / immunology
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Intestine, Small / metabolism
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Intestine, Small / microbiology
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Intestines / immunology
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Intestines / microbiology*
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Male
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Matrix Metalloproteinase 7 / genetics
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Matrix Metalloproteinase 7 / metabolism
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Metagenome
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Mice
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Mice, Inbred Strains
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Mice, Knockout
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Mice, Transgenic
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Microscopy, Fluorescence
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Phylogeny
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RNA, Ribosomal, 16S / genetics
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T-Lymphocytes, Helper-Inducer / cytology
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T-Lymphocytes, Helper-Inducer / immunology
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T-Lymphocytes, Helper-Inducer / metabolism
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alpha-Defensins / genetics
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alpha-Defensins / immunology
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alpha-Defensins / metabolism*
Substances
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Interleukin-17
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RNA, Ribosomal, 16S
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alpha-Defensins
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Matrix Metalloproteinase 7