Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Research Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Stem Cells. 2022 Mar 3;40(1):14-21. doi: 10.1093/stmcls/sxab007.
Balanced production of immune cells is critical for the maintenance of steady-state immune surveillance, and increased production of myeloid cells is sometimes necessary to eliminate pathogens. Hematopoietic stem and progenitor cell (HSPC) sensing of commensal microbes and invading pathogens has a notable impact on hematopoiesis. In this review, we examine how commensal microbes regulate bone marrow HSPC activity to maintain balanced hematopoiesis in the steady state, and how HSPCs proliferate and differentiate during emergency myelopoiesis in response to infection. HSPCs express a variety of pattern recognition receptors and cytokine receptors that they use to sense the presence of microbes, either directly via detection of microbial components and metabolites, or indirectly by responding to cytokines produced by other host cells. We describe direct and indirect mechanisms of microbial sensing by HSPCs and highlight evidence demonstrating long-term effects of acute and chronic microbial stimuli on HSPCs. We also discuss a possible connection between myeloid-biased hematopoiesis and elevated levels of circulating microbiome-derived components in the context of aging and metabolic stress. Finally, we highlight the prospect of trained immunity-based vaccines that could exploit microbial stimulation of HSPCs.
免疫细胞的平衡产生对于维持稳态免疫监视至关重要，有时需要增加髓样细胞的产生以消除病原体。造血干细胞和祖细胞（HSPC）对共生微生物和入侵病原体的感应对造血有显著影响。在这篇综述中，我们研究了共生微生物如何调节骨髓 HSPC 活性以在稳态下维持平衡的造血，以及 HSPC 在感染时如何增殖和分化以进行紧急髓样生成。HSPC 表达多种模式识别受体和细胞因子受体，它们用于直接通过检测微生物成分和代谢物，或间接通过响应其他宿主细胞产生的细胞因子来感知微生物的存在。我们描述了 HSPC 对微生物的直接和间接感应机制，并强调了急性和慢性微生物刺激对 HSPC 的长期影响的证据。我们还讨论了在衰老和代谢应激背景下，偏骨髓造血与循环微生物衍生成分水平升高之间可能存在的联系。最后，我们强调了基于训练免疫的疫苗的前景，这种疫苗可以利用微生物对 HSPC 的刺激。
