Aix Marseille University, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Centre d'Immunologie de Marseille-Luminy , Marseille, France.
Department of Anatomy, University of California, San Francisco , San Francisco, CA, USA.
J Exp Med. 2023 Jul 3;220(7). doi: 10.1084/jem.20210567. Epub 2023 Apr 17.
So far, hematopoietic stem cells (HSC) are considered the source of mature immune cells, the latter being the only ones capable of mounting an immune response. Recent evidence shows HSC can also directly sense cytokines released upon infection/inflammation and pathogen-associated molecular pattern interaction while keeping a long-term memory of previously encountered signals. Direct sensing of danger signals by HSC induces early myeloid commitment, increases myeloid effector cell numbers, and contributes to an efficient immune response. Here, by using specific genetic tools on both the host and pathogen sides, we show that HSC can directly sense B. abortus pathogenic bacteria within the bone marrow via the interaction of the cell surface protein CD150 with the bacterial outer membrane protein Omp25, inducing efficient functional commitment of HSC to the myeloid lineage. This is the first demonstration of direct recognition of a live pathogen by HSC via CD150, which attests to a very early contribution of HSC to immune response.
迄今为止，造血干细胞（HSC）被认为是成熟免疫细胞的来源，而后者是唯一能够引发免疫反应的细胞。最近的证据表明，HSC 还可以直接感知感染/炎症时释放的细胞因子和病原体相关分子模式的相互作用，同时保持对先前遇到的信号的长期记忆。HSC 对危险信号的直接感知诱导早期髓样细胞的定向分化，增加髓样效应细胞的数量，并有助于有效的免疫反应。在这里，我们通过在宿主和病原体双方使用特定的遗传工具，表明 HSC 可以通过细胞表面蛋白 CD150 与细菌外膜蛋白 Omp25 的相互作用，直接感知骨髓中的 B. abortus 致病菌，从而有效地将 HSC 定向分化为髓系细胞。这是首次通过 CD150 直接识别活病原体的证明，证明了 HSC 对免疫反应的早期贡献。
