SARS-CoV-2 induces human plasmacytoid predendritic cell diversification via UNC93B and IRAK4-Reference-Cited by-同舟云学术

SARS-CoV-2 induces human plasmacytoid predendritic cell diversification via UNC93B and IRAK4

Published:2021-01-28 Issue:4 Volume:218 Page:
ISSN:0022-1007
Container-title:Journal of Experimental Medicine
language:en
Short-container-title:

Author:

Onodi Fanny¹^ORCID,Bonnet-Madin Lucie²^ORCID,Meertens Laurent²^ORCID,Karpf Léa¹^ORCID,Poirot Justine¹^ORCID,Zhang Shen-Ying³⁴⁵^ORCID,Picard Capucine⁴⁶^ORCID,Puel Anne³⁴⁵^ORCID,Jouanguy Emmanuelle³⁴⁵^ORCID,Zhang Qian⁵^ORCID,Le Goff Jérôme¹⁷^ORCID,Molina Jean-Michel²⁷^ORCID,Delaugerre Constance²⁷^ORCID,Casanova Jean-Laurent³⁴⁵⁸^ORCID,Amara Ali²^ORCID,Soumelis Vassili¹⁹^ORCID

Affiliation:

1. Université de Paris, Institut de Recherche Saint-Louis, Institut National de la Santé et de la Recherche Médicale U976, Hôpital Saint-Louis, Paris, France

2. Université de Paris, Institut de Recherche Saint-Louis, Institut National de la Santé et de la Recherche Médicale U944, Centre National de la Recherche Scientifique 7212, Hôpital Saint-Louis, Paris, France

3. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, Necker Hospital for Sick Children, Paris, France

4. Université de Paris, Institut National de la Santé et de la Recherche Médicale Unite Mixte de Recherche 1163, Institut Imagine, Paris, France

5. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY

6. Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, Assistance Publique–Hôpitaux de Paris, Paris, France

7. Laboratoire de Virologie et Département des Maladies Infectieuses, Hôpital Saint-Louis, Assistance Publique–Hôpitaux de Paris, Paris, France

8. Howard Hughes Medical Institute, New York, NY

9. Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Laboratoire d'Immunologie, Paris, France

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 predendritic cells (pDCs), a key player in antiviral immunity. We show that pDCs 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.

Funder

French Government

Fondation pour la Recherche Médicale

Agence Nationale de la Recherche

Université de Paris

Howard Hughes Medical Institute

Rockefeller University

St. Giles Foundation

Institut National de la Santé et de la Recherche Médicale

French Foundation for Medical Research

French National Research Agency

Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence