Journal article

Infection Mobilizes Hematopoietic Stem Cells through Cooperative NOD-like Receptor and Toll-like Receptor Signaling

Aaron Burberry, Melody Y Zeng, Lei Ding, Ian Wicks, Naohiro Inohara, Sean J Morrison, Gabriel Nunez

Cell Host & Microbe | CELL PRESS | Published : 2014

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 s..

View full abstract

Grants

Awarded by Training Program in Organogenesis


Awarded by National Institutes of Health



Awarded by EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT


Awarded by NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES


Funding Acknowledgements

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.