Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Curr Opin Hematol. 2019 Jul;26(4):207-213. doi: 10.1097/MOH.0000000000000511.
The innate immune system is essential in the protection against microbial infection and facilitating tissue repair mechanisms. During these stresses, the maintenance of innate immune cell numbers through stress-induced or emergency hematopoiesis is key for our survival. One major mechanism to recognize danger signals is through the activation of Toll-like receptors (TLRs) on the surface of hematopoietic cells, including hematopoietic stem cell (HSC) and hematopoietic progenitor cell (HPC), and nonhematopoietic cells, which recognize pathogen-derived or damaged-induced compounds and can influence the emergency hematopoietic response. This review explores how direct pathogen-sensing by HSC/HPC regulates hematopoiesis, and the positive and negative consequences of these signals.
Recent studies have highlighted new roles for TLRs in regulating HSC and HPC differentiation to innate immune cells of both myeloid and lymphoid origin and augmenting HSC and HPC migration capabilities. Most interestingly, new insights as to how acute versus chronic stimulation of TLR signaling regulates HSC and HPC function has been explored.
Recent evidence suggests that TLRs may play an important role in many inflammation-associated diseases. This suggests a possible use for TLR agonists or antagonists as potential therapeutics. Understanding the direct effects of TLR signaling by HSC and HPC may help regulate inflammatory/danger signal-driven emergency hematopoiesis.
先天免疫系统对于抵抗微生物感染和促进组织修复机制至关重要。在这些压力下，通过应激诱导或应急造血来维持先天免疫细胞数量对于我们的生存是关键。识别危险信号的一个主要机制是通过激活造血细胞（包括造血干细胞[HSC]和造血祖细胞[HPC]）和非造血细胞表面的 Toll 样受体（TLRs），这些受体可以识别病原体衍生或损伤诱导的化合物，并能影响应急造血反应。这篇综述探讨了 HSC/HPC 如何直接感知病原体来调节造血，以及这些信号的积极和消极影响。
最近的研究强调了 TLR 在调节 HSC 和 HPC 分化为髓系和淋巴系固有免疫细胞以及增强 HSC 和 HPC 迁移能力方面的新作用。最有趣的是，人们探索了急性和慢性 TLR 信号刺激如何调节 HSC 和 HPC 功能的新见解。
最近的证据表明，TLRs 可能在许多与炎症相关的疾病中发挥重要作用。这表明 TLR 激动剂或拮抗剂可能作为潜在的治疗药物。了解 HSC 和 HPC 中 TLR 信号的直接作用可能有助于调节炎症/危险信号驱动的应急造血。
