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 Núñez

Research output: Contribution to journalArticle

64 Scopus citations

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-/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.

Original languageEnglish (US)
Pages (from-to)779-791
Number of pages13
JournalCell Host and Microbe
Volume15
Issue number6
DOIs
Publication statusPublished - Jun 11 2014

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ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

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