Nonproductive exposure of PBMCs to SARS‐CoV‐2 induces cell‐intrinsic innate immune responses
Abstract Cell‐intrinsic responses mounted in PBMCs during mild and severe COVID‐19 differ quantitatively and qualitatively. Whether they are triggered by signals emitted by productively infected cells of the respiratory tract or result from physical interaction with virus particles remains unclear....
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2022-08-01
|
| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/msb.202210961 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849235399182909440 |
|---|---|
| author | Julia Kazmierski Kirstin Friedmann Dylan Postmus Jackson Emanuel Cornelius Fischer Jenny Jansen Anja Richter Laure Bosquillon de Jarcy Christiane Schüler Madlen Sohn Sascha Sauer Christian Drosten Antoine‐Emmanuel Saliba Leif Erik Sander Marcel A Müller Daniela Niemeyer Christine Goffinet |
| author_facet | Julia Kazmierski Kirstin Friedmann Dylan Postmus Jackson Emanuel Cornelius Fischer Jenny Jansen Anja Richter Laure Bosquillon de Jarcy Christiane Schüler Madlen Sohn Sascha Sauer Christian Drosten Antoine‐Emmanuel Saliba Leif Erik Sander Marcel A Müller Daniela Niemeyer Christine Goffinet |
| author_sort | Julia Kazmierski |
| collection | DOAJ |
| description | Abstract Cell‐intrinsic responses mounted in PBMCs during mild and severe COVID‐19 differ quantitatively and qualitatively. Whether they are triggered by signals emitted by productively infected cells of the respiratory tract or result from physical interaction with virus particles remains unclear. Here, we analyzed susceptibility and expression profiles of PBMCs from healthy donors upon ex vivo exposure to SARS‐CoV and SARS‐CoV‐2. In line with the absence of detectable ACE2 receptor expression, human PBMCs were refractory to productive infection. RT–PCR experiments and single‐cell RNA sequencing revealed JAK/STAT‐dependent induction of interferon‐stimulated genes (ISGs) but not proinflammatory cytokines. This SARS‐CoV‐2‐specific response was most pronounced in monocytes. SARS‐CoV‐2‐RNA‐positive monocytes displayed a lower ISG signature as compared to bystander cells of the identical culture. This suggests a preferential invasion of cells with a low ISG baseline profile or delivery of a SARS‐CoV‐2‐specific sensing antagonist upon efficient particle internalization. Together, nonproductive physical interaction of PBMCs with SARS‐CoV‐2‐ and, to a much lesser extent, SARS‐CoV particles stimulate JAK/STAT‐dependent, monocyte‐accentuated innate immune responses that resemble those detected in vivo in patients with mild COVID‐19. |
| format | Article |
| id | doaj-art-bd2eb001419145ec893ee0b1a1a9d093 |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2022-08-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-bd2eb001419145ec893ee0b1a1a9d0932025-08-20T04:02:49ZengSpringer NatureMolecular Systems Biology1744-42922022-08-0118811610.15252/msb.202210961Nonproductive exposure of PBMCs to SARS‐CoV‐2 induces cell‐intrinsic innate immune responsesJulia Kazmierski0Kirstin Friedmann1Dylan Postmus2Jackson Emanuel3Cornelius Fischer4Jenny Jansen5Anja Richter6Laure Bosquillon de Jarcy7Christiane Schüler8Madlen Sohn9Sascha Sauer10Christian Drosten11Antoine‐Emmanuel Saliba12Leif Erik Sander13Marcel A Müller14Daniela Niemeyer15Christine Goffinet16Institute of Virology, Campus Charité Mitte, Charité – Universitätsmedizin BerlinInstitute of Virology, Campus Charité Mitte, Charité – Universitätsmedizin BerlinInstitute of Virology, Campus Charité Mitte, Charité – Universitätsmedizin BerlinInstitute of Virology, Campus Charité Mitte, Charité – Universitätsmedizin BerlinScientific Genomics Platforms, Laboratory of Functional Genomics, Nutrigenomics and Systems Biology, Max Delbrück Center for Molecular MedicineInstitute of Virology, Campus Charité Mitte, Charité – Universitätsmedizin BerlinInstitute of Virology, Campus Charité Mitte, Charité – Universitätsmedizin BerlinInstitute of Virology, Campus Charité Mitte, Charité – Universitätsmedizin BerlinInstitute of Virology, Campus Charité Mitte, Charité – Universitätsmedizin BerlinScientific Genomics Platforms, Laboratory of Functional Genomics, Nutrigenomics and Systems Biology, Max Delbrück Center for Molecular MedicineScientific Genomics Platforms, Laboratory of Functional Genomics, Nutrigenomics and Systems Biology, Max Delbrück Center for Molecular MedicineInstitute of Virology, Campus Charité Mitte, Charité – Universitätsmedizin BerlinHelmholtz Institute for RNA‐based Infection Research (HIRI), Helmholtz‐Center for Infection Research (HZI)Department of Infectious Diseases and Respiratory Medicine, Charité ‐ Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin, and Berlin Institute of Health (BIH)Institute of Virology, Campus Charité Mitte, Charité – Universitätsmedizin BerlinInstitute of Virology, Campus Charité Mitte, Charité – Universitätsmedizin BerlinInstitute of Virology, Campus Charité Mitte, Charité – Universitätsmedizin BerlinAbstract Cell‐intrinsic responses mounted in PBMCs during mild and severe COVID‐19 differ quantitatively and qualitatively. Whether they are triggered by signals emitted by productively infected cells of the respiratory tract or result from physical interaction with virus particles remains unclear. Here, we analyzed susceptibility and expression profiles of PBMCs from healthy donors upon ex vivo exposure to SARS‐CoV and SARS‐CoV‐2. In line with the absence of detectable ACE2 receptor expression, human PBMCs were refractory to productive infection. RT–PCR experiments and single‐cell RNA sequencing revealed JAK/STAT‐dependent induction of interferon‐stimulated genes (ISGs) but not proinflammatory cytokines. This SARS‐CoV‐2‐specific response was most pronounced in monocytes. SARS‐CoV‐2‐RNA‐positive monocytes displayed a lower ISG signature as compared to bystander cells of the identical culture. This suggests a preferential invasion of cells with a low ISG baseline profile or delivery of a SARS‐CoV‐2‐specific sensing antagonist upon efficient particle internalization. Together, nonproductive physical interaction of PBMCs with SARS‐CoV‐2‐ and, to a much lesser extent, SARS‐CoV particles stimulate JAK/STAT‐dependent, monocyte‐accentuated innate immune responses that resemble those detected in vivo in patients with mild COVID‐19.https://doi.org/10.15252/msb.202210961interferoninterferon‐stimulated genesPBMCsSARS‐CoV‐2 |
| spellingShingle | Julia Kazmierski Kirstin Friedmann Dylan Postmus Jackson Emanuel Cornelius Fischer Jenny Jansen Anja Richter Laure Bosquillon de Jarcy Christiane Schüler Madlen Sohn Sascha Sauer Christian Drosten Antoine‐Emmanuel Saliba Leif Erik Sander Marcel A Müller Daniela Niemeyer Christine Goffinet Nonproductive exposure of PBMCs to SARS‐CoV‐2 induces cell‐intrinsic innate immune responses Molecular Systems Biology interferon interferon‐stimulated genes PBMCs SARS‐CoV‐2 |
| title | Nonproductive exposure of PBMCs to SARS‐CoV‐2 induces cell‐intrinsic innate immune responses |
| title_full | Nonproductive exposure of PBMCs to SARS‐CoV‐2 induces cell‐intrinsic innate immune responses |
| title_fullStr | Nonproductive exposure of PBMCs to SARS‐CoV‐2 induces cell‐intrinsic innate immune responses |
| title_full_unstemmed | Nonproductive exposure of PBMCs to SARS‐CoV‐2 induces cell‐intrinsic innate immune responses |
| title_short | Nonproductive exposure of PBMCs to SARS‐CoV‐2 induces cell‐intrinsic innate immune responses |
| title_sort | nonproductive exposure of pbmcs to sars cov 2 induces cell intrinsic innate immune responses |
| topic | interferon interferon‐stimulated genes PBMCs SARS‐CoV‐2 |
| url | https://doi.org/10.15252/msb.202210961 |
| work_keys_str_mv | AT juliakazmierski nonproductiveexposureofpbmcstosarscov2inducescellintrinsicinnateimmuneresponses AT kirstinfriedmann nonproductiveexposureofpbmcstosarscov2inducescellintrinsicinnateimmuneresponses AT dylanpostmus nonproductiveexposureofpbmcstosarscov2inducescellintrinsicinnateimmuneresponses AT jacksonemanuel nonproductiveexposureofpbmcstosarscov2inducescellintrinsicinnateimmuneresponses AT corneliusfischer nonproductiveexposureofpbmcstosarscov2inducescellintrinsicinnateimmuneresponses AT jennyjansen nonproductiveexposureofpbmcstosarscov2inducescellintrinsicinnateimmuneresponses AT anjarichter nonproductiveexposureofpbmcstosarscov2inducescellintrinsicinnateimmuneresponses AT laurebosquillondejarcy nonproductiveexposureofpbmcstosarscov2inducescellintrinsicinnateimmuneresponses AT christianeschuler nonproductiveexposureofpbmcstosarscov2inducescellintrinsicinnateimmuneresponses AT madlensohn nonproductiveexposureofpbmcstosarscov2inducescellintrinsicinnateimmuneresponses AT saschasauer nonproductiveexposureofpbmcstosarscov2inducescellintrinsicinnateimmuneresponses AT christiandrosten nonproductiveexposureofpbmcstosarscov2inducescellintrinsicinnateimmuneresponses AT antoineemmanuelsaliba nonproductiveexposureofpbmcstosarscov2inducescellintrinsicinnateimmuneresponses AT leiferiksander nonproductiveexposureofpbmcstosarscov2inducescellintrinsicinnateimmuneresponses AT marcelamuller nonproductiveexposureofpbmcstosarscov2inducescellintrinsicinnateimmuneresponses AT danielaniemeyer nonproductiveexposureofpbmcstosarscov2inducescellintrinsicinnateimmuneresponses AT christinegoffinet nonproductiveexposureofpbmcstosarscov2inducescellintrinsicinnateimmuneresponses |