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Cell Host Microbe. 2014 Jun 11;15(6):779-91. doi: 10.1016/j.chom.2014.05.004. Epub 2014 May 29.

Infection mobilizes hematopoietic stem cells through cooperative NOD-like receptor and Toll-like receptor signaling.

Author information

1
Department of Pathology and Comprehensive Cancer Center, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109, USA.
2
Department of Rehabilitation and Regenerative Medicine, Department of Microbiology and Immunology, Columbia Stem Cell Initiative, Columbia University Medical Center, 630 W. 168 Street, P & S, 7-513, New York, NY 10032, USA.
3
Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Victoria 3052, Australia.
4
Howard Hughes Medical Institute, Children's Research Institute, Department of Pediatrics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
5
Department of Pathology and Comprehensive Cancer Center, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109, USA. Electronic address: gabriel.nunez@umich.edu.

Abstract

Adult hematopoietic stem cells (HSCs) are maintained in specialized niches within the bone marrow under steady-state conditions and mobilize 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(-/low)Sca1+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.

Comment in

PMID:
24882704
PMCID:
PMC4085166
DOI:
10.1016/j.chom.2014.05.004
[Indexed for MEDLINE]
Free PMC Article

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