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. 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.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
Nonproductive exposure of PBMCs to SARS‐CoV ‐2 induces cell‐intrinsic innate immune responses ; volume:18 ; number:8 ; year:2022 ; extent:20
Molecular systems biology ; 18, Heft 8 (2022) (gesamt 20)

Urheber
Kazmierski, Julia
Friedmann, Kirstin
Postmus, Dylan
Emanuel, Jackson
Fischer, Cornelius
Jansen, Jenny
Richter, Anja
Bosquillon de Jarcy, Laure
Schüler, Christiane
Sohn, Madlen
Sauer, Sascha
Drosten, Christian
Saliba, Antoine‐Emmanuel
Sander, Leif Erik
Müller, Marcel A.
Niemeyer, Daniela
Laqmani-Goffinet, Christine

DOI
10.15252/msb.202210961
URN
urn:nbn:de:101:1-2022081715291275748679
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:20 MESZ

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