Infection mobilizes hematopoietic stem cells through cooperative NOD-like receptor and Toll-like receptor signaling.
Infection mobilizes hematopoietic stem cells through cooperative NOD-like receptor and Toll-like receptor signaling.
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DOI：
10.1016/j.chom.2014.05.004
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发表时间：
2014-06-11
影响因子：
30.3
通讯作者：
Núñez G
中科院分区：
文献类型：
--
作者：
Burberry A;Zeng MY;Ding L;Wicks I;Inohara N;Morrison SJ;Núñez G
成体造血干细胞（HSC）在稳态条件下维持在骨髓内的专门小生境中，并且在诸如细菌感染的应激期间被动员用于髓外造血。然而，其潜在机制尚不清楚。我们发现，大肠杆菌全身感染小鼠，通常与人类菌血症，动员功能性造血干细胞脾脏。在TLR 4缺陷和RIPK 2缺陷小鼠中，脾脏HSC（CD 150 + CD 48-Lin−/lowScal 1 +cKit+）的积聚减少，这一过程涉及TLR和细胞溶质NOD 1/NOD 2信号传导。因此，在放射抗性细胞中单独的NOD 1和TLR 4的双重刺激足以动员HSC，而HSC上的TLR 4表达被抑制。机制上，TLR 4和NOD 1协同诱导粒细胞集落刺激因子（G-CSF），这是髓外HSC积累所需的。动员的HSC和祖细胞产生中性粒细胞和单核细胞，并有助于限制继发感染。
Adult hematopoietic stem cells (HSCs) are maintained in specialized niches within the bone marrow under steady-state conditions and mobilized for extramedullary hematopoiesis during periods of stress such as bacterial infections. However, the underlying mechanisms are unclear. We show that systemic infection of mice with Escherichia coli, commonly associated with bacteremia in humans, mobilizes functional HSCs to the spleen. Accumulation of splenic HSCs (CD150+CD48-Lin−/lowScal1+cKit+) was diminished in TLR4-deficient and RIPK2-deficient mice, implicating TLRs and cytosolic NOD1/NOD2 signaling in the process. Accordingly, dual stimulation of NOD1 and TLR4 in radio-resistant cells alone was sufficient to mobilize HSCs, while TLR4 expression on HSCs was dispensable. Mechanistically, TLR4 and NOD1 synergistically induced granulocyte-colony stimulating factor (G-CSF), which was required for extramedullary HSC accumulation. Mobilized HSCs and progenitor cells gave rise to neutrophils and monocytes and contributed to limiting secondary infection.
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影响因子：
64.5
作者：
Kiel, MJ;Yilmaz, ÖH;Morrison, SJ
通讯作者：
Morrison, SJ
DOI：
10.1073/pnas.94.5.1908
发表时间：
1997-03-04
影响因子：
11.1
作者：
Morrison, SJ;Wright, DE;Weissman, IL
通讯作者：
Weissman, IL
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
3.1
作者：
Johns, J. L.;MacNamara, K. C.;Borjesson, D. L.
通讯作者：
Borjesson, D. L.
影响因子：
8.7
作者：
Franchi L;Warner N;Viani K;Nuñez G
通讯作者：
Nuñez G