Abstract
Several studies have analyzed antiviral immune pathways in late-stage severe COVID-19. However, the initial steps of SARS-CoV-2 antiviral immunity are poorly understood. Here, we have isolated primary SARS-CoV-2 viral strains, and studied their interaction with human plasmacytoid pre-dendritic cells (pDC), a key player in antiviral immunity. We show that pDC are not productively infected by SARS-CoV-2. However, they efficiently diversified into activated P1-, P2-, and P3-pDC effector subsets in response to viral stimulation. They expressed CD80, CD86, CCR7, and OX40 ligand at levels similar to influenza virus-induced activation. They rapidly produced high levels of interferon-α, interferon-λ1, IL-6, IP-10, and IL-8. All major aspects of SARS-CoV-2-induced pDC activation were inhibited by hydroxychloroquine. Mechanistically, SARS-CoV-2-induced pDC activation critically depended on IRAK4 and UNC93B1, as established using pDC from genetically deficient patients. Overall, our data indicate that human pDC are efficiently activated by SARS-CoV-2 particles and may thus contribute to type I IFN-dependent immunity against SARS-CoV-2 infection.
Competing Interest Statement
The authors have declared no competing interest.
Abbreviations
- CBA
- Cytometric bead array
- COVID-19
- Coronavirus disease 2019
- CPE
- Cytopathogenic effects
- DC
- Dendritic cell
- Flu
- Influenza virus A
- HCQ
- Hydroxychloroquine
- HD
- Healthy donor
- IFN
- Interferon
- MERS
- Middle East respiratory syndrome coronavirus
- MFI
- Mean fluorescence intensity
- MHV
- Murine hepatitis virus
- MOI
- Multiplicity of infection
- N
- nucleoprotein antigen
- OD
- optical density
- PBMC
- Peripheral blood mononuclear cells
- pDC
- Plasmacytoid pre-dendritic cells
- SARS-CoV-2
- Severe Acute Respiratory Syndrome-Coronavirus-2
- TLR
- Toll-like receptor