西班牙国家心血管研究中心（CNIC）David Sancho等研究人员合作发现，肠道屏障破坏后微生物群转位，促进Mincle介导的骨髓中髓系祖细胞训练。2025年1月22日，《免疫》杂志在线发表了这项成果。

研究人员揭示了在小鼠给予硫酸葡聚糖钠（DSS）后肠道通透性增加所引发的先天免疫反应。研究人员发现，粪肠球菌（Enterococcus faecalis）在DSS处理后转移到骨髓，并在骨髓衍生的鼠巨噬细胞和人单核细胞中诱导了训练免疫（TI）的标志。DSS处理或热杀的E. faecalis重编程了骨髓祖细胞（BMP），导致体外和体内炎症反应增强，并在随后的病原感染中提供保护。

C型凝集素受体Mincle（Clec4e）对于E. faecalis诱导的TI在BMPs中的发生至关重要。Clec4e^−/−小鼠在E. faecalis处理后表现出TI受损，并在DSS处理后减少病理表现。因此，Mincle对E. faecalis的感知诱导了TI，这可能对与肠道通透性增加相关的病理具有长期影响。

研究人员表示，肠道屏障受损后，常驻细菌可系统性地转移，诱发宿主的促炎症状态。

附：英文原文

Title: Microbiota translocation following intestinal barrier disruption promotes Mincle-mediated training of myeloid progenitors in the bone marrow

Author: Iaki Robles-Vera, Aitor Jarit-Cabanillas, Paola Brandi, María Martínez-López, Sarai Martínez-Cano, Manuel Rodrigo-Tapias, Marcos Femenía-Muia, Ana Redondo-Urzainqui, Vanesa Nuez, Cristina González-Correa, Javier Moleón, Juan Duarte, Laura Conejero, Pablo Mata-Martínez, Carmen María Díez-Rivero, Marta Bergón-Gutiérrez, Iván Fernández-López, Manuel J. Gómez, Ana Quintas, Ana Dopazo, Fátima Sánchez-Cabo, Esther Pariente, Carlos del Fresno, José Luis Subiza, Salvador Iborra, David Sancho

Issue&Volume: 2025-01-22

Abstract: Impairment of the intestinal barrier allows the systemic translocation of commensal bacteria, inducing a proinflammatory state in the host. Here, we investigated innate immune responses following increased gut permeability upon administration of dextran sulfate sodium (DSS) in mice. We found that Enterococcus faecalis translocated to the bone marrow following DSS treatment and induced trained immunity (TI) hallmarks in bone-marrow-derived mouse macrophages and human monocytes. DSS treatment or heat-killed E. faecalis reprogrammed bone marrow progenitors (BMPs), resulting in enhanced inflammatory responses in vitro and in vivo and protection against subsequent pathogen infections. The C-type lectin receptor Mincle (Clec4e) was essential for E. faecalis-induced TI in BMPs. Clec4e/ mice showed impaired TI upon E. faecalis administration and reduced pathology following DSS treatment. Thus, Mincle sensing of E. faecalis induces TI that may have long-term effects on pathologies associated with increased gut permeability.

DOI: 10.1016/j.immuni.2024.12.012

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00577-6