Human α-Defensin 6 Promotes Mucosal Innate Immunity Through Self-Assembled Peptide Nanonets

被引：322

作者：

Chu, Hiutung ^{[1
]}

Pazgier, Marzena ^{[2
,3
]}

Jung, Grace ^{[4
]}

Nuccio, Sean-Paul ^{[1
]}

Castillo, Patricia A. ^{[1
]}

de Jong, Maarten F. ^{[1
]}

Winter, Maria G. ^{[1
]}

Winter, Sebastian E. ^{[1
]}

Wehkamp, Jan ^{[1
]}

Shen, Bo ^{[5
]}

Salzman, Nita H. ^{[6
]}

Underwood, Mark A. ^{[7
]}

Tsolis, Renee M. ^{[1
]}

Young, Glenn M. ^{[8
]}

Lu, Wuyuan ^{[2
,3
]}

Lehrer, Robert I. ^{[4
]}

Baeumler, Andreas J. ^{[1
]}

Bevins, Charles L. ^{[1
]}

机构：

[1] Univ Calif Davis, Sch Med, Dept Microbiol & Immunol, Davis, CA 95616 USA

[2] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA

[3] Univ Maryland, Sch Med, Dept Biochem Mol Biol, Baltimore, MD 21201 USA

[4] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA

[5] Cleveland Clin Fdn, Dept Gastroenterol & Hepatol, Cleveland, OH 44195 USA

[6] Med Coll Wisconsin, Dept Pediat, Div Gastroenterol, Milwaukee, WI 53226 USA

[7] Univ Calif Davis, Sch Med, Dept Pediat, Davis, CA 95616 USA

[8] Univ Calif Davis, Dept Food Sci & Technol, Davis, CA 95616 USA

来源：

SCIENCE | 2012年 / 337卷 / 6093期

基金：

美国国家卫生研究院;

关键词：

PANETH CELLS; MICE; HD5;

D O I：

10.1126/science.1218831

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Defensins are antimicrobial peptides that contribute broadly to innate immunity, including protection of mucosal tissues. Human alpha-defensin (HD) 6 is highly expressed by secretory Paneth cells of the small intestine. However, in contrast to the other defensins, it lacks appreciable bactericidal activity. Nevertheless, we report here that HD6 affords protection against invasion by enteric bacterial pathogens in vitro and in vivo. After stochastic binding to bacterial surface proteins, HD6 undergoes ordered self-assembly to form fibrils and nanonets that surround and entangle bacteria. This self-assembly mechanism occurs in vivo, requires histidine-27, and is consistent with x-ray crystallography data. These findings support a key role for HD6 in protecting the small intestine against invasion by diverse enteric pathogens and may explain the conservation of HD6 throughout Hominidae evolution.

引用

页码：477 / 481

页数：5

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