SARS-CoV-2 evades immune detection in alveolar macrophages

Louise Dalskov; Michelle Møhlenberg; Jacob Thyrsted; Julia Blay-Cadanet; Ebbe Toftgaard Poulsen; Birgitte Holst Folkersen; Søren Helbo Skaarup; David Olagnier; Line Reinert; Jan Johannes Enghild; Hans Jürgen Hoffmann; Christian Kanstrup Holm; Rune Hartmann

doi:10.15252/embr.202051252

SARS-CoV-2 evades immune detection in alveolar macrophages

Louise Dalskov, Michelle Møhlenberg, Jacob Thyrsted, Julia Blay-Cadanet, Ebbe Toftgaard Poulsen, Birgitte Holst Folkersen, Søren Helbo Skaarup, David Olagnier, Line Reinert, Jan Johannes Enghild, Hans Jürgen Hoffmann, Christian Kanstrup Holm, Rune Hartmann^*

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

58 Citations (Scopus)

Abstract

Respiratory infections, like the current COVID-19 pandemic, target epithelial cells in the respiratory tract. Alveolar macrophages (AMs) are tissue-resident macrophages located within the lung. They play a key role in the early phases of an immune response to respiratory viruses. AMs are likely the first immune cells to encounter SARS-CoV-2 during an infection, and their reaction to the virus will have a profound impact on the outcome of the infection. Interferons (IFNs) are antiviral cytokines and among the first cytokines produced upon viral infection. In this study, AMs from non-infectious donors are challenged with SARS-CoV-2. We demonstrate that challenged AMs are incapable of sensing SARS-CoV-2 and of producing an IFN response in contrast to other respiratory viruses, like influenza A virus and Sendai virus, which trigger a robust IFN response. The absence of IFN production in AMs upon challenge with SARS-CoV-2 could explain the initial asymptotic phase observed during COVID-19 and argues against AMs being the sources of pro-inflammatory cytokines later during infection.

Original language	English
Article number	e51252
Journal	EMBO Reports
Volume	21
Issue	12
ISSN	1469-221X
DOIs	https://doi.org/10.15252/embr.202051252
Publication status	Published - Dec 2020

Keywords

COVID-19
SARS-CoV-2
alveolar macrophages
interferon
interferon lambda

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645910/pdf/EMBR-21-e51252.pdf

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title = "SARS-CoV-2 evades immune detection in alveolar macrophages",

abstract = "Respiratory infections, like the current COVID-19 pandemic, target epithelial cells in the respiratory tract. Alveolar macrophages (AMs) are tissue-resident macrophages located within the lung. They play a key role in the early phases of an immune response to respiratory viruses. AMs are likely the first immune cells to encounter SARS-CoV-2 during an infection, and their reaction to the virus will have a profound impact on the outcome of the infection. Interferons (IFNs) are antiviral cytokines and among the first cytokines produced upon viral infection. In this study, AMs from non-infectious donors are challenged with SARS-CoV-2. We demonstrate that challenged AMs are incapable of sensing SARS-CoV-2 and of producing an IFN response in contrast to other respiratory viruses, like influenza A virus and Sendai virus, which trigger a robust IFN response. The absence of IFN production in AMs upon challenge with SARS-CoV-2 could explain the initial asymptotic phase observed during COVID-19 and argues against AMs being the sources of pro-inflammatory cytokines later during infection.",

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author = "Louise Dalskov and Michelle M{\o}hlenberg and Jacob Thyrsted and Julia Blay-Cadanet and Poulsen, {Ebbe Toftgaard} and Folkersen, {Birgitte Holst} and Skaarup, {S{\o}ren Helbo} and David Olagnier and Line Reinert and Enghild, {Jan Johannes} and Hoffmann, {Hans J{\"u}rgen} and Holm, {Christian Kanstrup} and Rune Hartmann",

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doi = "10.15252/embr.202051252",

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T1 - SARS-CoV-2 evades immune detection in alveolar macrophages

AU - Dalskov, Louise

AU - Møhlenberg, Michelle

AU - Thyrsted, Jacob

AU - Blay-Cadanet, Julia

AU - Poulsen, Ebbe Toftgaard

AU - Folkersen, Birgitte Holst

AU - Skaarup, Søren Helbo

AU - Olagnier, David

AU - Reinert, Line

AU - Enghild, Jan Johannes

AU - Hoffmann, Hans Jürgen

AU - Holm, Christian Kanstrup

AU - Hartmann, Rune

PY - 2020/12

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N2 - Respiratory infections, like the current COVID-19 pandemic, target epithelial cells in the respiratory tract. Alveolar macrophages (AMs) are tissue-resident macrophages located within the lung. They play a key role in the early phases of an immune response to respiratory viruses. AMs are likely the first immune cells to encounter SARS-CoV-2 during an infection, and their reaction to the virus will have a profound impact on the outcome of the infection. Interferons (IFNs) are antiviral cytokines and among the first cytokines produced upon viral infection. In this study, AMs from non-infectious donors are challenged with SARS-CoV-2. We demonstrate that challenged AMs are incapable of sensing SARS-CoV-2 and of producing an IFN response in contrast to other respiratory viruses, like influenza A virus and Sendai virus, which trigger a robust IFN response. The absence of IFN production in AMs upon challenge with SARS-CoV-2 could explain the initial asymptotic phase observed during COVID-19 and argues against AMs being the sources of pro-inflammatory cytokines later during infection.

AB - Respiratory infections, like the current COVID-19 pandemic, target epithelial cells in the respiratory tract. Alveolar macrophages (AMs) are tissue-resident macrophages located within the lung. They play a key role in the early phases of an immune response to respiratory viruses. AMs are likely the first immune cells to encounter SARS-CoV-2 during an infection, and their reaction to the virus will have a profound impact on the outcome of the infection. Interferons (IFNs) are antiviral cytokines and among the first cytokines produced upon viral infection. In this study, AMs from non-infectious donors are challenged with SARS-CoV-2. We demonstrate that challenged AMs are incapable of sensing SARS-CoV-2 and of producing an IFN response in contrast to other respiratory viruses, like influenza A virus and Sendai virus, which trigger a robust IFN response. The absence of IFN production in AMs upon challenge with SARS-CoV-2 could explain the initial asymptotic phase observed during COVID-19 and argues against AMs being the sources of pro-inflammatory cytokines later during infection.

KW - COVID-19

KW - SARS-CoV-2

KW - alveolar macrophages

KW - interferon

KW - interferon lambda

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DO - 10.15252/embr.202051252

M3 - Journal article

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SN - 1469-221X

VL - 21

JO - EMBO Reports

JF - EMBO Reports

IS - 12

M1 - e51252

ER -

SARS-CoV-2 evades immune detection in alveolar macrophages

Abstract

Keywords

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