Two subsets of dendritic cell (DCs), plasmacytoid (p) and myeloid (m) DCs, have been described in humans and mice. These subsets are known to have divergent roles during an immune response, but their developmental course is unclear. Here we report that virus infection induces bone marrow pDCs to differentiate into mDCs, thereby undergoing profound phenotypic and functional changes including the acquisition of enhanced antigen-presenting capacity and the ability to recognize different microbial structures through Toll-like receptor 4. The conversion of pDCs into mDCs is also induced by the injection of double-stranded RNA and requires type I interferons. Our results establish a precursor-product developmental relationship between these two DC subsets and highlight unexpected plasticity of bone marrow pDCs.
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This is publication no. 16635-NP from the Division of Virology, Department of Neuropharmacology, TSRI. We thank A. O'Garra and A. Boonstra for suggestions; Amgen for human recombinant Flt3L; and personnel of the TSRI Flow Cytometry Facility, especially C. Silao, for technical assistance with cell sorting. This work was supported by grants from the US Public Health Service (AI45927 and AI09484). E.I.Z. was supported by Pew Foundation Latin American Fellowship and Fundacion Antorchas.
The authors declare no competing financial interests.
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Zuniga, E., McGavern, D., Pruneda-Paz, J. et al. Bone marrow plasmacytoid dendritic cells can differentiate into myeloid dendritic cells upon virus infection. Nat Immunol 5, 1227–1234 (2004). https://doi.org/10.1038/ni1136
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