tetano
Editor, Senior Moderator
Cell Discov
. 2021 Apr 13;7(1):24.
doi: 10.1038/s41421-021-00258-1.
Distinct uptake, amplification, and release of SARS-CoV-2 by M1 and M2 alveolar macrophages
Jiadi Lv[SUP] #[/SUP][SUP] 1 [/SUP], Zhenfeng Wang[SUP] #[/SUP][SUP] 1 [/SUP], Yajin Qu[SUP] #[/SUP][SUP] 2 [/SUP], Hua Zhu[SUP] 2 [/SUP], Qiangqiang Zhu[SUP] 1 [/SUP], Wei Tong[SUP] 2 [/SUP], Linlin Bao[SUP] 2 [/SUP], Qi Lv[SUP] 2 [/SUP], Ji Cong[SUP] 2 [/SUP], Dan Li[SUP] 2 [/SUP], Wei Deng[SUP] 2 [/SUP], Pin Yu[SUP] 2 [/SUP], Jiangping Song[SUP] 3 [/SUP], Wei-Min Tong[SUP] 4 [/SUP], Jiangning Liu[SUP] 5 [/SUP], Yuying Liu[SUP] 6 7 [/SUP], Chuan Qin[SUP] 8 [/SUP], Bo Huang[SUP] 9 10 11 [/SUP]
Affiliations
Abstract
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.
. 2021 Apr 13;7(1):24.
doi: 10.1038/s41421-021-00258-1.
Distinct uptake, amplification, and release of SARS-CoV-2 by M1 and M2 alveolar macrophages
Jiadi Lv[SUP] #[/SUP][SUP] 1 [/SUP], Zhenfeng Wang[SUP] #[/SUP][SUP] 1 [/SUP], Yajin Qu[SUP] #[/SUP][SUP] 2 [/SUP], Hua Zhu[SUP] 2 [/SUP], Qiangqiang Zhu[SUP] 1 [/SUP], Wei Tong[SUP] 2 [/SUP], Linlin Bao[SUP] 2 [/SUP], Qi Lv[SUP] 2 [/SUP], Ji Cong[SUP] 2 [/SUP], Dan Li[SUP] 2 [/SUP], Wei Deng[SUP] 2 [/SUP], Pin Yu[SUP] 2 [/SUP], Jiangping Song[SUP] 3 [/SUP], Wei-Min Tong[SUP] 4 [/SUP], Jiangning Liu[SUP] 5 [/SUP], Yuying Liu[SUP] 6 7 [/SUP], Chuan Qin[SUP] 8 [/SUP], Bo Huang[SUP] 9 10 11 [/SUP]
Affiliations
- PMID: 33850112
- DOI: 10.1038/s41421-021-00258-1
Abstract
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.