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Blood. 2013 Sep 5;122(10):1770-8. doi: 10.1182/blood-2012-11-466268. Epub 2013 Jul 18.

Staphylococcus aureus recognition by hematopoietic stem and progenitor cells via TLR2/MyD88/PGE2 stimulates granulopoiesis in wounds.

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Department of Veterinary Clinical Sciences, University of Minnesota College of Veterinary Medicine, St. Paul, MN;


During bacterial infection, hematopoietic stem and progenitor cells (HSPCs) differentiate into polymorphonuclear leukocytes (PMNs) in the bone marrow. We reported that HSPCs recruited to Staphylococcus aureus-infected skin wounds in mice undergo granulopoiesis, whereas other authors have demonstrated their differentiation in vitro after Toll-like receptor 2 (TLR2)/MyD88 stimulation. Here, we examined this pathway in HSPC trafficking and granulopoiesis within S aureus-infected wounds. Lineage- HSPCs from TLR2- or MyD88-deficient mice injected into infected wounds of wild-type (WT) mice exhibited impaired granulopoiesis. However, HSPCs from WT mice produced similar numbers of PMNs whether transferred into wounds of TLR2-, MyD88-deficient, or WT mice. Prostaglandin E2 (PGE2), which stimulates HSPC survival and proliferation, was produced by HSPCs after TLR2 stimulation, suggesting that TLR2/MyD88 activation promotes granulopoiesis in part by production and autocrine activity of PGE2. Pretreatment of TLR2- or MyD88-deficient HSPCs with PGE2 rescued granulocytic differentiation in vivo. Finally, we demonstrate that bone marrow-derived lin-/Sca-1+/c-kit+ cells produced PGE2 and underwent granulopoiesis after TLR2 stimulation. lin-/Sca-1+/c-kit+ cells deficient in TLR2 or MyD88 produced PMNs after PGE2 treatment when transferred into uninfected wounds. We conclude that granulopoiesis in S aureus-infected wounds is induced by TLR2/MyD88 activation of HSPCs through a mechanism that involves autocrine production and activity of PGE2.

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