Enteric defensins are essential regulators of intestinal microbial ecology

被引:910
作者
Salzman, Nita H. [1 ,4 ]
Hung, Kuiechun [1 ,4 ]
Haribhai, Dipica [2 ,3 ,4 ]
Chu, Hiutung [5 ]
Karlsson-Sjoeberg, Jenny [5 ]
Amir, Elad [1 ,4 ]
Teggatz, Paul [1 ,4 ]
Barman, Melissa [1 ,4 ]
Hayward, Michael [1 ,4 ]
Eastwood, Daniel [6 ]
Stoel, Maaike [7 ]
Zhou, Yanjiao [8 ]
Sodergren, Erica [8 ]
Weinstock, George M. [8 ]
Bevins, Charles L. [5 ]
Williams, Calvin B. [2 ,3 ,4 ]
Bos, Nicolaas A. [7 ]
机构
[1] Med Coll Wisconsin, Div Gastroenterol, Milwaukee, WI 53226 USA
[2] Med Coll Wisconsin, Div Rheumatol, Milwaukee, WI 53226 USA
[3] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA
[4] Med Coll Wisconsin, Childrens Res Inst, Milwaukee, WI 53226 USA
[5] Univ Calif Davis, Sch Med, Dept Microbiol & Immunol, Davis, CA 95616 USA
[6] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA
[7] Univ Groningen, Univ Med Ctr Groningen, Immunol Sect, Dept Cell Biol, NL-9700 AB Groningen, Netherlands
[8] Washington Univ, Sch Med, Dept Genet, Genome Ctr, St Louis, MO 63110 USA
基金
美国国家卫生研究院;
关键词
SEGMENTED FILAMENTOUS BACTERIA; DISTAL GUT MICROBIOME; PANETH CELL; ANTIMICROBIAL PEPTIDES; IMMUNE-RESPONSE; INNATE IMMUNITY; MOUSE; DISEASE; MICE; COLONIZATION;
D O I
10.1038/ni.1825
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:76 / U1
页数:8
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[1]   Enteric salmonellosis disrupts the microbial ecology of the murine gastrointestinal tract [J].
Barman, Melissa ;
Unold, David ;
Shifley, Kathleen ;
Amir, Elad ;
Hung, Kueichun ;
Bos, Nicolaas ;
Salzman, Nita .
INFECTION AND IMMUNITY, 2008, 76 (03) :907-915
[2]   A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells [J].
Cadwell, Ken ;
Liu, John Y. ;
Brown, Sarah L. ;
Miyoshi, Hiroyuki ;
Loh, Joy ;
Lennerz, Jochen K. ;
Kishi, Chieko ;
Kc, Wumesh ;
Carrero, Javier A. ;
Hunt, Steven ;
Stone, Christian D. ;
Brunt, Elizabeth M. ;
Xavier, Ramnik J. ;
Sleckman, Barry P. ;
Li, Ellen ;
Mizushima, Noboru ;
Stappenbeck, Thaddeus S. ;
Virgin, Herbert W. .
NATURE, 2008, 456 (7219) :259-U62
[3]  
Canny G, 2006, METH MOL B, V341, P17
[4]   Prolonged Impact of Antibiotics on Intestinal Microbial Ecology and Susceptibility to Enteric Salmonella Infection [J].
Croswell, Amy ;
Amir, Elad ;
Teggatz, Paul ;
Barman, Melissa ;
Salzman, Nita H. .
INFECTION AND IMMUNITY, 2009, 77 (07) :2741-2753
[5]   Diversity of the human intestinal microbial flora [J].
Eckburg, PB ;
Bik, EM ;
Bernstein, CN ;
Purdom, E ;
Dethlefsen, L ;
Sargent, M ;
Gill, SR ;
Nelson, KE ;
Relman, DA .
SCIENCE, 2005, 308 (5728) :1635-1638
[6]   Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system [J].
Garrett, Wendy S. ;
Lord, Graham M. ;
Punit, Shivesh ;
Lugo-Villarino, Geanncarlo ;
Mazmanian, Sarkis K. ;
Ito, Susumu ;
Glickman, Jonathan N. ;
Glimcher, Laurie H. .
CELL, 2007, 131 (01) :33-45
[7]   Metalloproteinases and their inhibitors: Regulators of wound healing [J].
Gill, Sean E. ;
Parks, William C. .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2008, 40 (6-7) :1334-1347
[8]   Metagenomic analysis of the human distal gut microbiome [J].
Gill, Steven R. ;
Pop, Mihai ;
DeBoy, Robert T. ;
Eckburg, Paul B. ;
Turnbaugh, Peter J. ;
Samuel, Buck S. ;
Gordon, Jeffrey I. ;
Relman, David A. ;
Fraser-Liggett, Claire M. ;
Nelson, Karen E. .
SCIENCE, 2006, 312 (5778) :1355-1359
[9]   Functional reprogramming of the primary immune response by T cell receptor antagonism [J].
Haribhai, D ;
Edwards, B ;
Williams, ML ;
Williams, CB .
JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 200 (11) :1371-1382
[10]   Segmented filamentous bacteria prevent colonization of enteropathogenic Escherichia coli O103 in rabbits [J].
Heczko, U ;
Abe, A ;
Finlay, BB .
JOURNAL OF INFECTIOUS DISEASES, 2000, 181 (03) :1027-1033