TY - JOUR
T1 - Infection mobilizes hematopoietic stem cells through cooperative NOD-like receptor and toll-like receptor signaling
AU - Burberry, Aaron
AU - Zeng, Melody Y.
AU - Ding, Lei
AU - Wicks, Ian
AU - Inohara, Naohiro
AU - Morrison, Sean J.
AU - Núñez, Gabriel
N1 - Funding Information:
We would like to thank L. Franchi and B. Moore for helpful discussions. We would like to thank J. Whitfield of the University of Michigan Immunology Core for preforming ELISAs and Mizuho Hasegawa for providing E. coli strain NI491. Flow cytometry costs were partially defrayed by the University of Michigan Cancer Center. A.B. was partially supported by the Training Program in Organogenesis grant T32HD007505. M.Y.Z. was supported by Training Grant T32DK094775. This work was supported by grant RO1 DK61707 from the National Institutes of Health to G.N.
PY - 2014/6/11
Y1 - 2014/6/11
N2 - 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-/lowSca1+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.
AB - 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-/lowSca1+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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U2 - 10.1016/j.chom.2014.05.004
DO - 10.1016/j.chom.2014.05.004
M3 - Article
C2 - 24882704
AN - SCOPUS:84902436102
SN - 1931-3128
VL - 15
SP - 779
EP - 791
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 6
ER -