Innate Immune Functions of α-Defensins in the Small Intestine

被引:39
作者
Bevins, Charles L. [1 ]
机构
[1] Univ Calif Davis, Sch Med, Dept Microbiol & Immunol, Davis, CA 95616 USA
关键词
Defensin; Microbiota; Paneth cells; Innate immunity; INFLAMMATORY-BOWEL-DISEASE; ILEAL CROHNS-DISEASE; PANETH CELLS; ANTIMICROBIAL PEPTIDES; GUT MICROBIOTA; SUSCEPTIBILITY; ASSOCIATION; SECRETION; RESPONSES; VARIANTS;
D O I
10.1159/000354681
中图分类号
R57 [消化系及腹部疾病];
学科分类号
100201 [内科学];
摘要
The intestinal mucosa interfaces with a complex, dense community of microorganisms, including hundreds of species of resident microbiota and many transient microbes entering from food- and water-borne sources. In the small intestine, Paneth cells (specialized secretory epithelial cells) produce abundant quantities of alpha-defensins and several other antibiotic peptides. Human Paneth cells make two alpha-defensins: HD5 and HD6. Data from in vivo models indicate that Paneth cell alpha-defensins play a pivotal role in defense from food- and water-borne pathogens in the intestine. The mechanism by which these two a-defensins protect from enteric pathogens is quite distinct. HD5 is a potent antimicrobial that kills target microbes by membrane disruption, whereas HD6 is newly discovered to self-assemble to form fibrils and nanonets that surround and entangle bacteria. Recent data suggest that HD5 also serves to help shape the composition of the colonizing microbiota. Studies in humans suggest that reduced expression of HD5 and HD6 is a fundamental feature of ileal Crohn's disease. Mechanistically, the link between reduced Paneth cell alpha-defensin expression and ileal Crohn's disease pathogenesis may be a result of the weakened mucosal antimicrobial defense and/or alterations in the composition of commensal microbiota. (C) 2013 S.Karger AG, Basel
引用
收藏
页码:299 / 304
页数:6
相关论文
共 41 条
[1]
CRS-peptides: unique defense peptides of mouse Paneth cells [J].
Andersson, M. L. ;
Karlsson-Sjoberg, J. M. T. ;
Putsep, K. L-A .
MUCOSAL IMMUNOLOGY, 2012, 5 (04) :367-376
[2]
Modulation of mouse Paneth cell α-defensin secretion by mIKCa1, a Ca2+-activated, intermediate conductance potassium channel [J].
Ayabe, T ;
Wulff, H ;
Darmoul, D ;
Cahalan, MD ;
Chandy, KG ;
Ouellette, AJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (05) :3793-3800
[3]
Secretion of microbicidal α-defensins by intestinal Paneth cells in response to bacteria [J].
Ayabe, T ;
Satchell, DP ;
Wilson, CL ;
Parks, WC ;
Selsted, ME ;
Ouellette, AJ .
NATURE IMMUNOLOGY, 2000, 1 (02) :113-118
[4]
Host responses to the human microbiome [J].
Baeckhed, Fredrik .
NUTRITION REVIEWS, 2012, 70 :S14-S17
[5]
The potter's wheel: the host's role in sculpting its microbiota [J].
Bevins, Charles L. ;
Salzman, Nita H. .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2011, 68 (22) :3675-3685
[6]
Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis [J].
Bevins, Charles L. ;
Salzman, Nita H. .
NATURE REVIEWS MICROBIOLOGY, 2011, 9 (05) :356-368
[7]
Human α-Defensin 6 Promotes Mucosal Innate Immunity Through Self-Assembled Peptide Nanonets [J].
Chu, Hiutung ;
Pazgier, Marzena ;
Jung, Grace ;
Nuccio, Sean-Paul ;
Castillo, Patricia A. ;
de Jong, Maarten F. ;
Winter, Maria G. ;
Winter, Sebastian E. ;
Wehkamp, Jan ;
Shen, Bo ;
Salzman, Nita H. ;
Underwood, Mark A. ;
Tsolis, Renee M. ;
Young, Glenn M. ;
Lu, Wuyuan ;
Lehrer, Robert I. ;
Baeumler, Andreas J. ;
Bevins, Charles L. .
SCIENCE, 2012, 337 (6093) :477-481
[8]
Paneth Cells: Maestros of the Small Intestinal Crypts [J].
Clevers, Hans C. ;
Bevins, Charles L. .
ANNUAL REVIEW OF PHYSIOLOGY, VOL 75, 2013, 75 :289-311
[9]
Antibacterial activity and specificity of the six human α-defensins [J].
Ericksen, B ;
Wu, ZB ;
Lu, WY ;
Lehrer, RI .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2005, 49 (01) :269-275
[10]
The role of the gut microbiota in nutrition and health [J].
Flint, Harry J. ;
Scott, Karen P. ;
Louis, Petra ;
Duncan, Sylvia H. .
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, 2012, 9 (10) :577-589