Enteric defensins are essential regulators of intestinal microbial ecology.
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.
Division of Gastroenterology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA. nsalzman@mcw.edu
Nita H
NH
Salzman
Kuiechun
K
Hung
Dipica
D
Haribhai
Hiutung
H
Chu
Jenny
J
Karlsson-Sjöberg
Elad
E
Amir
Paul
P
Teggatz
Melissa
M
Barman
Michael
M
Hayward
Daniel
D
Eastwood
Maaike
M
Stoel
Yanjiao
Y
Zhou
Erica
E
Sodergren
George M
GM
Weinstock
Charles L
CL
Bevins
Calvin B
CB
Williams
Nicolaas A
NA
Bos
D000818:Animals; D001419:Bacteria / Q000145:classification / Q000235:genetics / Q000254:growth & development; D015169:Colony Count, Microbial; D004463:Ecology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D007422:Intestines / Q000276:immunology / Q000382:microbiology*; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism; D054892:Metagenome; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D010802:Phylogeny; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D023084:alpha-Defensins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D020381:Interleukin-17; D012336:RNA, Ribosomal, 16S; D023084:alpha-Defensins; D020783:Matrix Metalloproteinase 7