Inflammatory Type 2 cDCs Acquire Features of cDC1s and Macrophages to Orchestrate Immunity to Respiratory Virus Infection.
Immunity
; 52(6): 1039-1056.e9, 2020 06 16.
Article
in English
| MEDLINE | ID: covidwho-209829
ABSTRACT
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
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Respirovirus Infections
/
Dendritic Cells
/
Cell Plasticity
/
Immunity
/
Macrophages
Type of study:
Prognostic study
Language:
English
Journal:
Immunity
Journal subject:
Allergy and Immunology
Year:
2020
Document Type:
Article
Affiliation country:
J.immuni.2020.04.005
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