Science：α-防御素6在肠道免疫中的重要作用

6月21日，Science在线报道了人α-防御素（HD）6在肠道免疫中的重要作用。

防御素是一种抗菌肽，它广泛地发挥促进先天免疫系统的功能，包括保护粘膜组织。人α-防御素（HD）6在小肠分泌性潘氏细胞高表达。然而，在对比其他防御素，它缺乏明显的杀菌活性。

尽管如此，本研究发现，在体外和体内实验中，HD6均可抵抗肠道细菌病原体的侵袭。随机地与细菌表面的蛋白质结合后，HD6经过有序自组装形成包围和纠缠细菌的小纤维和纳米网。这种自我组装机制发生在体内，需要组氨酸-27，并与X射线晶体学数据是一致的。

这些发现说明，在保护小肠免受多种肠道致病菌侵害过程中，HD6发挥关键作用，并可以解释整个人类进化中HD6的保守性。

doi:10.1016/j.cell.2011.10.017
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Human α-Defensin 6 Promotes Mucosal Innate Immunity Through Self-Assembled Peptide Nanonets

Hiutung Chu1, Marzena Pazgier2, Grace Jung3, Sean-Paul Nuccio1, Patricia A. Castillo1, Maarten F. de Jong1, Maria G. Winter1, Sebastian E. Winter1, Jan Wehkamp1,*, Bo Shen4, Nita H. Salzman5, Mark A. Underwood6, Renee M. Tsolis1, Glenn M. Young7, Wuyuan Lu2,?, Robert I. Lehrer3,?, Andreas J. B?umler1,?, Charles L. Bevins

Defensins are antimicrobial peptides that contribute broadly to innate immunity, including protection of mucosal tissues. Human α-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.