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Blood, 1 November 2008, Vol. 112, No. 9, pp. 3753-3761.
Prepublished online as a Blood First Edition Paper on June 13, 2008; DOI 10.1182/blood-2008-04-151506.
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Submitted April 14, 2008
Accepted May 23, 2008
Lymphoid precursors are directed to produce dendritic cells as a result of TLR9 ligation during herpes infection
Robert S. Welner, Rosana Pelayo, Yoshinori Nagai, Karla P. Garrett, Todd R. Wuest, Daniel J. Carr, Lisa A. Borghesi, Michael A. Farrar, and Paul W. Kincade*
Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States
Department of Ophthalmology and Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
Dept of Immunology, Univ of Pittsburgh, Pittsburgh, PA, United States
Center for Immunology and Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, United States
* Corresponding author; email: kincade{at}omrf.ouhsc.edu.
Hematopoietic stem and progenitor cells were previously found to express Toll-like receptors (TLR), suggesting that bacterial/viral products may influence blood cell formation. We now show that common lymphoid progenitors (CLPs) from mice with active HSV-1 infection are biased to dendritic cell (DC) differentiation, and the phenomenon is largely TLR9 dependent. Similarly, CLPs from mice treated with the TLR9 ligand CpG ODN had little ability to generate CD19+ B lineage cells and had augmented competence to generate DCs. TNF mediates the depletion of late-stage lymphoid progenitors from bone marrow in many inflammatory conditions, but re-direction of lymphopoiesis occurred in TNF-/- mice treated with CpG ODN. Increased numbers of DCs with a lymphoid past were identified in Ig gene recombination substrate reporter mice treated with CpG ODN. TLR9 is highly expressed on lymphoid progenitors, and culture studies revealed that those receptors rather than inflammatory cytokines, accounted for the production of several types of functional DCs. Common myeloid progenitors (CMP) are normally a good source of DCs, but this potential was reduced by TLR9 ligation. Thus, alternate differentiation pathways may be utilized to produce innate effector cells in health and disease.
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