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Distinct uptake, amplification, and release of SARS-CoV-2 by M1 and M2 alveolar macrophages

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invades the alveoli, where abundant alveolar macrophages (AMs) reside. How AMs respond to SARS-CoV-2 invasion remains elusive. Here, we show that classically activated M1 AMs facilitate viral spread; however, alternatively activated M2 AMs...

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Autores principales: Lv, Jiadi, Wang, Zhenfeng, Qu, Yajin, Zhu, Hua, Zhu, Qiangqiang, Tong, Wei, Bao, Linlin, Lv, Qi, Cong, Ji, Li, Dan, Deng, Wei, Yu, Pin, Song, Jiangping, Tong, Wei-Min, Liu, Jiangning, Liu, Yuying, Qin, Chuan, Huang, Bo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Singapore 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043100/
https://www.ncbi.nlm.nih.gov/pubmed/33850112
http://dx.doi.org/10.1038/s41421-021-00258-1
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author Lv, Jiadi
Wang, Zhenfeng
Qu, Yajin
Zhu, Hua
Zhu, Qiangqiang
Tong, Wei
Bao, Linlin
Lv, Qi
Cong, Ji
Li, Dan
Deng, Wei
Yu, Pin
Song, Jiangping
Tong, Wei-Min
Liu, Jiangning
Liu, Yuying
Qin, Chuan
Huang, Bo
author_facet Lv, Jiadi
Wang, Zhenfeng
Qu, Yajin
Zhu, Hua
Zhu, Qiangqiang
Tong, Wei
Bao, Linlin
Lv, Qi
Cong, Ji
Li, Dan
Deng, Wei
Yu, Pin
Song, Jiangping
Tong, Wei-Min
Liu, Jiangning
Liu, Yuying
Qin, Chuan
Huang, Bo
author_sort Lv, Jiadi
collection PubMed
description Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invades the alveoli, where abundant alveolar macrophages (AMs) reside. How AMs respond to SARS-CoV-2 invasion remains elusive. Here, we show that classically activated M1 AMs facilitate viral spread; however, alternatively activated M2 AMs limit the spread. M1 AMs utilize cellular softness to efficiently take up SARS-CoV-2. Subsequently, the invaded viruses take over the endo-lysosomal system to escape. M1 AMs have a lower endosomal pH, favoring membrane fusion and allowing the entry of viral RNA from the endosomes into the cytoplasm, where the virus achieves replication and is packaged to be released. In contrast, M2 AMs have a higher endosomal pH but a lower lysosomal pH, thus delivering the virus to lysosomes for degradation. In hACE2 transgenic mouse model, M1 AMs are found to facilitate SARS-CoV-2 infection of the lungs. These findings provide insights into the complex roles of AMs during SARS-CoV-2 infection, along with potential therapeutic targets.
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spelling pubmed-80431002021-04-14 Distinct uptake, amplification, and release of SARS-CoV-2 by M1 and M2 alveolar macrophages Lv, Jiadi Wang, Zhenfeng Qu, Yajin Zhu, Hua Zhu, Qiangqiang Tong, Wei Bao, Linlin Lv, Qi Cong, Ji Li, Dan Deng, Wei Yu, Pin Song, Jiangping Tong, Wei-Min Liu, Jiangning Liu, Yuying Qin, Chuan Huang, Bo Cell Discov Article Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invades the alveoli, where abundant alveolar macrophages (AMs) reside. How AMs respond to SARS-CoV-2 invasion remains elusive. Here, we show that classically activated M1 AMs facilitate viral spread; however, alternatively activated M2 AMs limit the spread. M1 AMs utilize cellular softness to efficiently take up SARS-CoV-2. Subsequently, the invaded viruses take over the endo-lysosomal system to escape. M1 AMs have a lower endosomal pH, favoring membrane fusion and allowing the entry of viral RNA from the endosomes into the cytoplasm, where the virus achieves replication and is packaged to be released. In contrast, M2 AMs have a higher endosomal pH but a lower lysosomal pH, thus delivering the virus to lysosomes for degradation. In hACE2 transgenic mouse model, M1 AMs are found to facilitate SARS-CoV-2 infection of the lungs. These findings provide insights into the complex roles of AMs during SARS-CoV-2 infection, along with potential therapeutic targets. Springer Singapore 2021-04-13 /pmc/articles/PMC8043100/ /pubmed/33850112 http://dx.doi.org/10.1038/s41421-021-00258-1 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Lv, Jiadi
Wang, Zhenfeng
Qu, Yajin
Zhu, Hua
Zhu, Qiangqiang
Tong, Wei
Bao, Linlin
Lv, Qi
Cong, Ji
Li, Dan
Deng, Wei
Yu, Pin
Song, Jiangping
Tong, Wei-Min
Liu, Jiangning
Liu, Yuying
Qin, Chuan
Huang, Bo
Distinct uptake, amplification, and release of SARS-CoV-2 by M1 and M2 alveolar macrophages
title Distinct uptake, amplification, and release of SARS-CoV-2 by M1 and M2 alveolar macrophages
title_full Distinct uptake, amplification, and release of SARS-CoV-2 by M1 and M2 alveolar macrophages
title_fullStr Distinct uptake, amplification, and release of SARS-CoV-2 by M1 and M2 alveolar macrophages
title_full_unstemmed Distinct uptake, amplification, and release of SARS-CoV-2 by M1 and M2 alveolar macrophages
title_short Distinct uptake, amplification, and release of SARS-CoV-2 by M1 and M2 alveolar macrophages
title_sort distinct uptake, amplification, and release of sars-cov-2 by m1 and m2 alveolar macrophages
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043100/
https://www.ncbi.nlm.nih.gov/pubmed/33850112
http://dx.doi.org/10.1038/s41421-021-00258-1
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