BACKGROUND Enteric antimicrobial peptides secreted from Paneth cells, including alpha-defensins (in mice named cryptdins), are key effector molecules of innate immunity in the small intestine. The importance of Paneth cells alpha-defensins emerged from studies of enteric bacterial infection in genetically modified mice, as well as from recent studies linking reduced levels of these alpha-defensins to Crohn's disease localized to the ileum. However, analysis of expression of Paneth cell alpha-defensins is incomplete. We therefore performed a comprehensive evaluation of the distribution of antimicrobial molecules along the mouse small intestinal tract to identify potential variations in regional expression. RESULTS In conventionally reared mice, the repertoire of Paneth cell antimicrobials differs between duodenum and ileum. In contrast to the uniform expression of most Paneth cell antimicrobials, both cryptdin 4 and cryptdin-related sequences (CRS) 4C peptides were expressed at progressively increasing amounts (101- and 104-fold, respectively) comparing duodenum and ileum. In tissues other than the small intestine, expression of CRS peptides was noted in thymus and caecum. Most Paneth cell products were also produced in the small intestine of germ-free mice at levels similar to those in controls, however CRS4C and RegIIIgamma had reduced levels in the former (3- and 8-fold, respectively). No significant changes in expression levels of Paneth cell antimicrobial peptides was observed after oral challenge with either Salmonella enterica serovar typhimurium or Listeria monocytogenes, supporting current notions on the constitutive nature of this defensive system. CONCLUSION The repertoire of antimicrobial peptides changes along the small intestinal tract, and a subset of these molecules are up-regulated upon colonization, but not in response to enteric bacterial pathogens. The changes detected upon colonization suggest that Paneth cell antimicrobial peptides may play an important role in commensal microbial homeostasis, in addition to their proposed role in protection against infection. In addition, the differential expression of CRS4C along the small intestine suggests mechanisms of regulation that are distinct from other Paneth cell derived antimicrobial peptides.

中文翻译：

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Paneth细胞抗菌肽沿小鼠肠道表达的区域变化。

背景从潘氏细胞分泌的肠道抗菌肽，包括α-防御素（在小鼠中称为隐蛋白），是小肠先天免疫的关键效应分子。Paneth 细胞 α-防御素的重要性源于对转基因小鼠肠道细菌感染的研究，以及最近将这些 α-防御素水平降低与位于回肠的克罗恩病联系起来的研究。然而，对潘氏细胞α-防御素表达的分析是不完整的。因此，我们对抗菌分子沿小鼠小肠的分布进行了全面评估，以确定区域表达的潜在变化。结果 在常规饲养的小鼠中，十二指肠和回肠之间的潘氏细胞抗微生物剂库不同。与大多数 Paneth 细胞抗菌剂的均匀表达相反，与十二指肠和回肠相比，cryptdin 4 和 cryptdin 相关序列 (CRS) 4C 肽的表达量逐渐增加（分别为 101 和 104 倍）。在小肠以外的组织中，在胸腺和盲肠中观察到 CRS 肽的表达。大多数 Paneth 细胞产物也在无菌小鼠的小肠中产生，其水平与对照组相似，但前者的 CRS4C 和 RegIIIgamma 水平降低（分别为 3 倍和 8 倍）。口服沙门氏菌鼠伤寒沙门氏菌或单核细胞增生李斯特氏菌后，没有观察到潘氏细胞抗微生物肽的表达水平发生显着变化，这支持了目前关于该防御系统组成性质的观点。结论 抗微生物肽的库沿小肠发生变化，其中一部分分子在定植时上调，但对肠道细菌病原体没有反应。定植后检测到的变化表明，潘氏细胞抗菌肽可能在共生微生物稳态中发挥重要作用，除了它们在预防感染方面的拟议作用。此外，CRS4C 沿小肠的差异表达表明调节机制不同于其他潘氏细胞衍生的抗菌肽。定植后检测到的变化表明，潘氏细胞抗菌肽可能在共生微生物稳态中发挥重要作用，除了它们在预防感染方面的拟议作用。此外，CRS4C 沿小肠的差异表达表明调节机制不同于其他潘氏细胞衍生的抗菌肽。定植后检测到的变化表明，潘氏细胞抗菌肽可能在共生微生物稳态中发挥重要作用，除了它们在预防感染方面的拟议作用。此外，CRS4C 沿小肠的差异表达表明调节机制不同于其他潘氏细胞衍生的抗菌肽。