| Title: |
SARS-CoV2 infection in whole lung primarily targets macrophages that display subset-specific responses |
| Authors: |
Manh, Thien-Phong Vu; Gouin, Carla; de Wolf, Julien; Jouneau, Luc; Pascale, Florentina; Bevilacqua, Claudia; Ar Gouilh, Meriadeg, M.; Costa, Bruno Da; Chevalier, Christophe; Glorion, Matthieu; Urien, Celine; Estephan, Jérôme; Magnan, Antoine; Le Guen, Morgan; Marquant, Quentin; Descamps, Delphyne; Dalod, Marc; Schwartz-Cornil, Isabelle; Sage, Edouard |
| Contributors: |
Dynamique Microbienne associée aux Infections Urinaires et Respiratoires (DYNAMICURE); Université de Caen Normandie (UNICAEN); Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN); Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM); Service de Virologie CHU Caen; CHU Caen Normandie – Centre Hospitalier Universitaire de Caen Normandie (CHU Caen Normandie); Normandie Université (NU)-Normandie Université (NU); Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE); Hôpital Foch Suresnes; Université de Versailles Saint-Quentin-en-Yvelines (UVSQ); Virologie et Immunologie Moléculaires (VIM (UR 0892)); Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE); Centre d'Immunologie de Marseille - Luminy (CIML); Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Source: |
https://hal.inrae.fr/hal-04612462 ; 2025. |
| Publisher Information: |
CCSD |
| Publication Year: |
2025 |
| Collection: |
Université de Versailles Saint-Quentin-en-Yvelines: HAL-UVSQ |
| Subject Terms: |
[SDV]Life Sciences [q-bio] |
| Description: |
Deciphering the initial steps of SARS-CoV-2 infection, that influence COVID-19 outcomes, is challenging because animal models do not always reproduce human biological processes and in vitro systems do not recapitulate the histoarchitecture and cellular composition of respiratory tissues. To address this, we developed an innovative ex vivo model of whole human lung infection with SARS-CoV-2, leveraging a lung transplantation technique. Through single-cell RNA-seq, we identified that alveolar and monocyte-derived macrophages (AMs and MoMacs) were initial targets of the virus. Exposure of isolated lung AMs, MoMacs, classical monocytes and non-classical monocytes (ncMos) to SARS-CoV-2 variants revealed that while all subsets responded, MoMacs produced higher levels of inflammatory cytokines than AMs, and ncMos contributed the least. A Wuhan lineage appeared to be more potent than a D614G virus, in a dose-dependent manner. Amidst the ambiguity in the literature regarding the initial SARS-CoV-2 cell target, our study reveals that AMs and MoMacs are dominant primary entry points for the virus, and suggests that their responses may conduct subsequent injury, depending on their abundance, the viral strain and dose. Interfering on virus interaction with lung macrophages should be considered in prophylactic strategies. |
| Document Type: |
report |
| Language: |
English |
| DOI: |
10.21203/rs.3.rs-4576639/v1 |
| Availability: |
https://hal.inrae.fr/hal-04612462; https://hal.inrae.fr/hal-04612462v1/document; https://hal.inrae.fr/hal-04612462v1/file/479c205b-cc0c-48ae-bbcb-c6c70195f099.pdf; https://doi.org/10.21203/rs.3.rs-4576639/v1 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.CD67EEE2 |
| Database: |
BASE |