Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany.
MOTI-VATE Graduate School, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Nat Commun. 2021 Apr 1;12(1):2027. doi: 10.1038/s41467-021-22103-5.
The immune response to mycobacteria is characterized by granuloma formation, which features multinucleated giant cells as a unique macrophage type. We previously found that multinucleated giant cells result from Toll-like receptor-induced DNA damage and cell autonomous cell cycle modifications. However, the giant cell progenitor identity remained unclear. Here, we show that the giant cell-forming potential is a particular trait of monocyte progenitors. Common monocyte progenitors potently produce cytokines in response to mycobacteria and their immune-active molecules. In addition, common monocyte progenitors accumulate cholesterol and lipids, which are prerequisites for giant cell transformation. Inducible monocyte progenitors are so far undescribed circulating common monocyte progenitor descendants with high giant cell-forming potential. Monocyte progenitors are induced in mycobacterial infections and localize to granulomas. Accordingly, they exhibit important immunological functions in mycobacterial infections. Moreover, their signature trait of high cholesterol metabolism may be piggy-backed by mycobacteria to create a permissive niche.
分枝杆菌的免疫反应以肉芽肿形成为特征，其特征是多核巨细胞作为一种独特的巨噬细胞类型。我们之前发现多核巨细胞是由 Toll 样受体诱导的 DNA 损伤和细胞自主细胞周期改变引起的。然而，巨细胞前体的身份仍不清楚。在这里，我们表明巨细胞形成的潜力是单核细胞前体的一个特殊特征。常见的单核细胞前体在受到分枝杆菌及其免疫活性分子的刺激时，能强有力地产生细胞因子。此外，常见的单核细胞前体积累胆固醇和脂质，这是巨细胞转化的前提条件。诱导性单核细胞前体是目前尚未描述的具有高巨细胞形成潜力的循环常见单核细胞前体的后代。单核细胞前体在分枝杆菌感染中被诱导，并定位于肉芽肿中。因此，它们在分枝杆菌感染中具有重要的免疫学功能。此外，它们高胆固醇代谢的特征可能被分枝杆菌利用，以创造一个许可的小生境。
