魏茨曼科学研究所M. Biton小组近日取得一项新成果。经过不懈努力，他们提出了肠道干细胞中炎性小体驱动的分化程序可防止沙门氏菌感染。这一研究成果于2026年5月12日发表在国际顶尖学术期刊《自然—免疫学》上。

在这里，该研究团队确定了干细胞内在免疫机制，通过Lgr5⁺ ISCs检测细胞内沙门氏菌并激活炎性小体依赖性分化程序。通过使用荧光标记的肠炎沙门氏菌、单细胞转录组学、命运图谱、类器官模型和基因扰动，我们证明被侵入的ISCs会通过凋亡相关斑点样蛋白（Speck-like protein，含CARD结构域，ASC，由Pycard编码）介导的炎症小体信号传导，迅速重编程为富含抗菌肽的Paneth细胞。这种命运转换增强了上皮抗微生物能力并限制了病原体在隐窝中的持久性。这种反应是沙门氏菌特有的，在人类肠道类器官中是保守的。

此外，侵袭相关的转录特征在克罗恩病患者的ISCs中丰富。他们的研究结果表明，ISCs作为细菌入侵的主动传感器，通过炎症小体信号传导启动上皮重塑，突出了干细胞可塑性作为一线先天免疫策略。

据悉，肠干细胞（ISCs）对于维持上皮细胞更新和屏障完整性至关重要，但它们在协调防御肠道病原体中的作用尚不清楚。

附：英文原文

Title: An inflammasome-driven differentiation program in intestinal stem cells protects against Salmonella infection

Author: Lebon, S., Habshush Menachem, A., Davidzohn, N., Katz, A., Wigoda, N., Braun, T., Yahalomi, D., Rotkopf, R., Holiar, V., Dadosh, T., Levin-Zaidman, S., Dezorella, N., Goliand, I., Kupervaser, M., Leebhoff, S., Blumberger, N., Hoffman, D., Grunewald, M., Levin, Y., Haberman, Y., Hofree, M., Biton, M.

Issue&Volume: 2026-05-12

Abstract: Intestinal stem cells (ISCs) are essential for sustaining epithelial renewal and barrier integrity, yet their role in orchestrating defense against enteric pathogens remains unclear. Here we identify a stem cell-intrinsic immune mechanism whereby Lgr5+ ISCs detect intracellular Salmonellaenterica and activate an inflammasome-dependent differentiation program. Using fluorescent-labeled S.enterica, single-cell transcriptomics, fate mapping, organoid models, and genetic perturbations, we show that invaded ISCs undergo rapid reprogramming toward antimicrobial peptide-enriched Paneth cells via apoptosis-associated Speck-like protein containing a CARD (ASC, encoded by Pycard)-mediated inflammasome signaling. This fate switch enhances epithelial antimicrobial capacity and restricts pathogen persistence in the crypt. The response is Salmonella-specific and conserved in human intestinal organoids. Moreover, the invasion-associated transcriptional signature is enriched in ISCs from patients with Crohn’s disease. Our findings reveal that ISCs act as active sensors of bacterial invasion and initiate epithelial remodeling through inflammasome signaling, highlighting stem cell plasticity as a frontline innate immune strategy.

DOI: 10.1038/s41590-026-02514-6

Source: https://www.nature.com/articles/s41590-026-02514-6