Transient activation of hematopoietic stem and progenitor cells by IFNγ during acute bacterial infection.
Transient activation of hematopoietic stem and progenitor cells by IFNγ during acute bacterial infection.
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DOI：
10.1371/journal.pone.0028669
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Winslow GM
中科院分区：
文献类型：
--
作者：
MacNamara KC;Jones M;Martin O;Winslow GM
造血干细胞(HSCs)在感染过程中如何对炎症信号做出反应还不是很清楚。我们的研究使用了埃立克体病的小鼠模型，这是一种新出现的硬壳病，以解决感染如何影响造血功能。C57BL/6小鼠感染细胞内细菌，会导致贫血和血小板减少，与在人类埃立克体病患者中观察到的情况类似。在小鼠中，感染促进了骨髓生成，这一过程严重依赖于干扰素γ信号。在目前的研究中，我们证明E-mis感染也驱动了骨髓LIN阴性的SCA-1+cKit+(LSK)细胞的瞬时增殖和扩增，LSK是一组含有HSCs的祖细胞。骨髓中LSK群体的扩大与休眠的、长期重新填充的HSCs的丧失、植入的减少以及该群体中的髓系分化倾向有关。感染诱导的LSK细胞植入减少和髓样偏向是一过性的，在感染后第8天最为明显。感染诱导的变化伴随着更多分化的多能祖细胞的扩张，需要干扰素γ信号。因此，在急性感染期间，作为对炎症信号的反应，造血干细胞可以经历依赖干扰素γ的快速、瞬时的从休眠到活动的转变，表面上，为宿主提供额外的或更好地武装的固有细胞用于宿主防御。造血功能的类似变化可能是许多对公共卫生具有重要意义的不同感染的基础。
How hematopoietic stem cells (HSCs) respond to inflammatory signals during infections is not well understood. Our studies have used a murine model of ehrlichiosis, an emerging tick-born disease, to address how infection impacts hematopoietic function. Infection of C57BL/6 mice with the intracellular bacterium, Ehrlichia muris, results in anemia and thrombocytopenia, similar to what is observed in human ehrlichiosis patients. In the mouse, infection promotes myelopoiesis, a process that is critically dependent on interferon gamma (IFNγ) signaling. In the present study, we demonstrate that E. muris infection also drives the transient proliferation and expansion of bone marrow Lin-negative Sca-1+ cKit+ (LSK) cells, a population of progenitor cells that contains HSCs. Expansion of the LSK population in the bone marrow was associated with a loss of dormant, long-term repopulating HSCs, reduced engraftment, and a bias towards myeloid lineage differentiation within that population. The reduced engraftment and myeloid bias of the infection-induced LSK cells was transient, and was most pronounced on day 8 post-infection. The infection-induced changes were accompanied by an expansion of more differentiated multipotent progenitor cells, and required IFNγ signaling. Thus, in response to inflammatory signals elicited during acute infection, HSCs can undergo a rapid, IFNγ-dependent, transient shift from dormancy to activity, ostensibly, to provide the host with additional or better-armed innate cells for host defense. Similar changes in hematopoietic function likely underlie many different infections of public health importance.
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DOI：
10.4049/jimmunol.1001893
发表时间：
2011-01-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
MacNamara KC;Oduro K;Martin O;Jones DD;McLaughlin M;Choi K;Borjesson DL;Winslow GM
通讯作者：
Winslow GM
影响因子：
64.5
作者：
Kiel, MJ;Yilmaz, ÖH;Morrison, SJ
通讯作者：
Morrison, SJ
影响因子：
64.5
作者：
Wilson, Anne;Laurenti, Elisa;Trumpp, Andreas
通讯作者：
Trumpp, Andreas
影响因子：
3.1
作者：
MacNamara, Katherine C.;Racine, Rachael;Winslow, Gary M.
通讯作者：
Winslow, Gary M.
影响因子：
4.4
作者：
Scumpia, Philip O.;Kelly-Scumpia, Kindra M.;Moldawer, Lyle L.
通讯作者：
Moldawer, Lyle L.