Developmental switch of intestinal antimicrobial peptide expression.
Developmental switch of intestinal antimicrobial peptide expression.
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DOI：
10.1084/jem.20071022
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发表时间：
2008-01-21
影响因子：
15.3
通讯作者：
Hornef, Mathias W.
中科院分区：
文献类型：
--
作者：
Menard, Sandrine;Foerster, Valentina;Lotz, Michael;Guetle, Dominique;Duerr, Claudia U.;Gallo, Richard L.;Henriques-Normark, Birgitta;Puetsep, Katrin;Andersson, Mats;Glocker, Erik O.;Hornef, Mathias W.
潘氏细胞衍生的肠抗微生物肽提供保护免受肠道感染和维持肠道内稳态。然而，潘氏细胞仅在新生儿期后才进化，并且保护新生儿肠道的抗菌机制尚不明确。使用定量逆转录-聚合酶链反应，免疫组织学，反相高效液相色谱和质谱，我们分析了肠道上皮细胞在出生后的发展抗菌谱。令人惊讶的是，观察到组织蛋白酶相关的抗菌肽（CRAMP）的组成型表达，并在新生儿上皮细胞中鉴定出加工的抗菌活性形式。肽合成仅限于出生后的前两周，并随着干细胞增殖增加和上皮细胞沿沿着隐窝-绒毛轴迁移而逐渐消失。CRAMP对新生肠道病原体单核细胞增生李斯特菌的肠道细菌生长具有显著的保护作用。因此，我们描述了先天免疫效应子表达和解剖分布的完整发育开关的第一个例子。上皮细胞CRAMP表达可能有助于细菌定植和肠道内稳态的建立，并在出生后期间提供对肠道感染的保护。
Paneth cell–derived enteric antimicrobial peptides provide protection from intestinal infection and maintenance of enteric homeostasis. Paneth cells, however, evolve only after the neonatal period, and the antimicrobial mechanisms that protect the newborn intestine are ill defined. Using quantitative reverse transcription–polymerase chain reaction, immunohistology, reverse-phase high-performance liquid chromatography, and mass spectrometry, we analyzed the antimicrobial repertoire in intestinal epithelial cells during postnatal development. Surprisingly, constitutive expression of the cathelin-related antimicrobial peptide (CRAMP) was observed, and the processed, antimicrobially active form was identified in neonatal epithelium. Peptide synthesis was limited to the first two weeks after birth and gradually disappeared with the onset of increased stem cell proliferation and epithelial cell migration along the crypt–villus axis. CRAMP conferred significant protection from intestinal bacterial growth of the newborn enteric pathogen Listeria monocytogenes. Thus, we describe the first example of a complete developmental switch in innate immune effector expression and anatomical distribution. Epithelial CRAMP expression might contribute to bacterial colonization and the establishment of gut homeostasis, and provide protection from enteric infection during the postnatal period.
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