Mouse type I IFN-producing cells are immature APCs with plasmacytoid morphology

Abstract

We show here that mouse interferon-α (IFN-α)–producing cells (mIPCs) are a unique subset of immature antigen-presenting cells (APCs) that secrete IFN-α upon stimulation with viruses. mIPCs have a plasmacytoid morphology, can be stained with an antibody to Ly6G and Ly6C (anti-Ly6G/C) and are Ly6C+B220+CD11cloCD4+; unlike other dendritic cell subsets, however, they do not express CD8α or CD11b. Although mIPCs undergo apoptosis in vitro, stimulation with viruses, IFN-α or CpG oligonucleotides enhanced their survival and T cell stimulatory activity. In vivo, mIPCs were the main producers of IFN-α in cytomegalovirus-infected mice, as depletion of Ly6G+/C+ cells abrogated IFN-α production. mIPCs produced interleukin 12 (IL-12) in response to viruses and CpG oligodeoxynucleotides, but not bacterial products. Although different pathogens can selectively engage various APC subsets for IL-12 production, IFN-α production is restricted to mIPCs' response to viral infection.

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Figure 1: Isolation of mIPCs from spleen cells.
Figure 2: Surface phenotype of freshly sorted Ly6G/C+CD11c+Lin spleen mIPCs.
Figure 3: Morphology of freshly sorted Ly6G/C+CD11c+Lin cells.
Figure 4: Viability of spleen and bone marrow Ly6G/C+CD11c+Lin mIPCs after 24-h culture.
Figure 5: Surface phenotype of cultured mIPCs.
Figure 6: T cell stimulatory capacity of mIPCs.
Figure 7: Ly6G/C+CD11c+Lin spleen cells produce both IFN-α and IL-12.
Figure 8: In vivo depletion of Ly6G/C cells abrogates IFN-α production.

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Acknowledgements

We thank C. Caux for critical reading and C. Alexandre, D. Lepot and M. Vatan for editorial assistance. Supported by NIH grant CA41268 (to C. B.) and the Cancer Research Institute (to M. D.).

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Correspondence to Giorgio Trinchieri.

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Asselin-Paturel, C., Boonstra, A., Dalod, M. et al. Mouse type I IFN-producing cells are immature APCs with plasmacytoid morphology. Nat Immunol 2, 1144–1150 (2001) doi:10.1038/ni736

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