Immunity
Volume 52, Issue 6, 16 June 2020, Pages 1039-1056.e9
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Article
Inflammatory Type 2 cDCs Acquire Features of cDC1s and Macrophages to Orchestrate Immunity to Respiratory Virus Infection

https://doi.org/10.1016/j.immuni.2020.04.005Get rights and content
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Highlights

  • Type I interferon drives differentiation of inf-cDC2s that closely resemble MCs

  • Inf-cDC2s prime CD4+ and CD8+ T cells, whereas MCs lack APC function

  • Inf-cDC2s internalize antibody-complexed antigen via Fc receptors

  • IRF8 controls maturation gene module in inf-cDC2s

Summary

The phenotypic and functional dichotomy between IRF8+ type 1 and IRF4+ type 2 conventional dendritic cells (cDC1s and cDC2s, respectively) is well accepted; it is unknown how robust this dichotomy is under inflammatory conditions, when additionally monocyte-derived cells (MCs) become competent antigen-presenting cells (APCs). Using single-cell technologies in models of respiratory viral infection, we found that lung cDC2s acquired expression of the Fc receptor CD64 shared with MCs and of IRF8 shared with cDC1s. These inflammatory cDC2s (inf-cDC2s) were superior in inducing CD4+ T helper (Th) cell polarization while simultaneously presenting antigen to CD8+ T cells. When carefully separated from inf-cDC2s, MCs lacked APC function. Inf-cDC2s matured in response to cell-intrinsic Toll-like receptor and type 1 interferon receptor signaling, upregulated an IRF8-dependent maturation module, and acquired antigens via convalescent serum and Fc receptors. Because hybrid inf-cDC2s are easily confused with monocyte-derived cells, their existence could explain why APC functions have been attributed to MCs.

Keywords

dendritic cell
monocyte
transcription factor
IRF8
virus
CD64
inf-cDC2
inflammation
type 1 interferon
Fc receptor
convalescent serum

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These authors contributed equally

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These authors contributed equally

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