Bone marrow plasmacytoid dendritic cells can differentiate into myeloid dendritic cells upon virus infection

Abstract

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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Figure 1: Virus infection induces bone marrow pDCs to differentiate into mDCs.
Figure 2: Splenic pDCs show a more differentiated phenotype than do bone marrow pDCs.
Figure 3: Cell proliferation and validation of pDCs as precursors of mDCs.
Figure 4: Transformation of pDCs into mDCs is a two-step process.
Figure 5: Bone marrow pDCs undergo phenotypic and functional changes after differentiation.
Figure 6: pDC conversion generates bona fide mDCs.
Figure 7: Differentiation of pDCs into mDCs is dependent on type I IFN.

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Acknowledgements

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.

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Correspondence to Elina I Zuniga.

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Supplementary information

Supplementary Fig. 1

Expression of Ly6C and Gr-1 on pDCs. (PDF 180 kb)

Supplementary Fig. 2

Spleen pDCs from poly(I:C)-injected mice do not convert into mDCs. (PDF 130 kb)

Supplementary Fig. 3

FACS-purified BM CD11c+120G8+CD11bB220+Ly6C+ pDCs were obtained from Poly(I:C) injected mice. (PDF 114 kb)

Supplementary Fig. 4

mCDs derived from pDCs can respond to TLR-4 stimulation. (PDF 194 kb)

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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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