Department of Molecular Microbiology, Washington University School of Medicine , St. Louis, Missouri, USA.
Department of Microbiology, University of Chicago , Chicago, Illinois, USA.
Infect Immun. 2023 Oct 17;91(10):e0020123. doi: 10.1128/iai.00201-23. Epub 2023 Sep 27.
Hematopoietic stem and progenitor cells (HSPCs) play a vital role in the host response to infection through the rapid and robust production of mature immune cells. These HSPC responses can be influenced, directly and indirectly, by pathogens as well. Infection with () can drive lymphopoiesis through modulation of type I interferon (IFN) signaling. We have previously found that the presence of a drug resistance (DR)-conferring mutation in drives altered host-pathogen interactions and heightened type I IFN production . But the impacts of this DR mutation on host responses to infection, particularly the hematopoietic compartment, remain unexplored. Using a mouse model, we show that, while drug-sensitive infection induces expansion of HSPC subsets and a skew toward lymphopoiesis, DR infection fails to induce an expansion of these subsets and an accumulation of mature granulocytes in the bone marrow. Using single-cell RNA sequencing, we show that the HSCs from DR -infected mice fail to upregulate pathways related to cytokine signaling across all profiled HSC subsets. Collectively, our studies report a novel finding of a chronic infection that fails to induce a potent hematopoietic response that can be further investigated to understand pathogen-host interaction at the level of hematopoiesis.
造血干细胞和祖细胞 (HSPCs) 通过快速而强大的成熟免疫细胞的产生，在宿主对感染的反应中起着至关重要的作用。这些 HSPC 反应也可以直接或间接地受到病原体的影响。感染 () 可以通过调节 I 型干扰素 (IFN) 信号来驱动淋巴发生。我们之前发现，在 中存在赋予耐药性 (DR) 的突变会改变宿主-病原体相互作用并增加 I 型 IFN 的产生。但是，这种 DR 突变对 宿主对 感染的反应的影响，特别是造血细胞，仍未得到探索。使用小鼠模型，我们表明，虽然药物敏感的 感染诱导 HSPC 亚群的扩增和向淋巴发生的倾斜，但 DR 感染不能诱导这些亚群的扩增和成熟粒细胞在骨髓中的积累。通过单细胞 RNA 测序，我们表明，来自 DR 感染小鼠的 HSCs 未能上调所有分析的 HSC 亚群中与细胞因子信号相关的途径。总的来说，我们的研究报告了一种新的慢性感染现象，即未能诱导强烈的造血反应，这可以进一步研究，以了解造血水平上的病原体-宿主相互作用。
