tetano
Editor, Senior Moderator
Microbiol Spectr
. 2023 Nov 8:e0087823.
doi: 10.1128/spectrum.00878-23. Online ahead of print. Spatiotemporal observations of host-pathogen interactions in mucosa during SARS-CoV-2 infection indicate a protective role of ILC2s
Wei Hu[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Lu Meng[SUP] #[/SUP][SUP] 4 [/SUP], Chao Wang[SUP] #[/SUP][SUP] 1 2 [/SUP], Wenhan Lu[SUP] #[/SUP][SUP] 3 [/SUP], Xiaoyu Tong[SUP] 3 [/SUP], Rui Lin[SUP] 5 [/SUP], Tao Xu[SUP] 6 [/SUP], Liang Chen[SUP] 7 [/SUP], An Cui[SUP] 1 2 [/SUP], Xiaoqing Xu[SUP] 1 2 [/SUP], Anni Li[SUP] 1 2 [/SUP], Jia Tang[SUP] 1 2 [/SUP], Hongru Gao[SUP] 3 [/SUP], Zhenle Pei[SUP] 3 [/SUP], Ruonan Zhang[SUP] 3 [/SUP], Yicong Wang[SUP] 3 [/SUP], Yu Wang[SUP] 3 [/SUP], Wendong Han[SUP] 8 [/SUP], Ning Jiang[SUP] 5 [/SUP], Chenglong Xiong[SUP] 9 [/SUP], Yi Feng[SUP] 3 [/SUP], Kuinyu Lee[SUP] 3 [/SUP], Mingquan Chen[SUP] 1 2 [/SUP]
Affiliations
Innate lymphoid cells (ILCs) play a crucial role in mucosal protection and tissue homeostasis. However, the early mucosal defense mechanisms against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus have not been fully understood to date. This knowledge gap has motivated us to develop a coronavirus disease 2019-like mouse model to investigate the interactions between the virus, its receptor, and ILCs. In our study, we conducted intranasal challenges using pseudovirus expressing Spike (PSV-S) to examine the expression patterns of humanized ACE2 (chiACE2) and the transduction of PSV-S in lung and ileum tissues over a specified time period. Within a span of 72 hours, we observed an intense viral transduction induced by the spike protein, which was detected from the central bronchus to the bronchiole and alveolus in the lung (levels 3 to 8). Similarly, we observed the transduction of PSV-S in the villi and crypts of the ileum. Interestingly, our precise three-dimensional colocalization analysis revealed that only 73.74% ± 1.76% of the PSV-S transduction depended on chiACE2. Furthermore, type 2 innate lymphoid cells (ILC2s) exhibited the most pronounced activation in the gut mucosa. This finding indicates the significant role of ILC2s as contributors to the mucosal defense against viral infections. Our data shed light on the critical involvement of ILC2s and their intricate three-dimensional regulatory network in combating SARS-CoV-2 within the mucosa.IMPORTANCEOur study revealed the spatial interaction between humanized ACE2 and pseudovirus expressing Spike, emphasizing the role of type 2 innate lymphoid cells during the initial phase of viral infection. These findings provide a foundation for the development of mucosal vaccines and other treatment approaches for both pre- and post-infection management of coronavirus disease 2019.
Keywords: ILC2; SARS-CoV-2; mucosal immunity; tissue transparency and 3D imaging.
. 2023 Nov 8:e0087823.
doi: 10.1128/spectrum.00878-23. Online ahead of print. Spatiotemporal observations of host-pathogen interactions in mucosa during SARS-CoV-2 infection indicate a protective role of ILC2s
Wei Hu[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Lu Meng[SUP] #[/SUP][SUP] 4 [/SUP], Chao Wang[SUP] #[/SUP][SUP] 1 2 [/SUP], Wenhan Lu[SUP] #[/SUP][SUP] 3 [/SUP], Xiaoyu Tong[SUP] 3 [/SUP], Rui Lin[SUP] 5 [/SUP], Tao Xu[SUP] 6 [/SUP], Liang Chen[SUP] 7 [/SUP], An Cui[SUP] 1 2 [/SUP], Xiaoqing Xu[SUP] 1 2 [/SUP], Anni Li[SUP] 1 2 [/SUP], Jia Tang[SUP] 1 2 [/SUP], Hongru Gao[SUP] 3 [/SUP], Zhenle Pei[SUP] 3 [/SUP], Ruonan Zhang[SUP] 3 [/SUP], Yicong Wang[SUP] 3 [/SUP], Yu Wang[SUP] 3 [/SUP], Wendong Han[SUP] 8 [/SUP], Ning Jiang[SUP] 5 [/SUP], Chenglong Xiong[SUP] 9 [/SUP], Yi Feng[SUP] 3 [/SUP], Kuinyu Lee[SUP] 3 [/SUP], Mingquan Chen[SUP] 1 2 [/SUP]
Affiliations
- PMID: 37937994
- DOI: 10.1128/spectrum.00878-23
Innate lymphoid cells (ILCs) play a crucial role in mucosal protection and tissue homeostasis. However, the early mucosal defense mechanisms against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus have not been fully understood to date. This knowledge gap has motivated us to develop a coronavirus disease 2019-like mouse model to investigate the interactions between the virus, its receptor, and ILCs. In our study, we conducted intranasal challenges using pseudovirus expressing Spike (PSV-S) to examine the expression patterns of humanized ACE2 (chiACE2) and the transduction of PSV-S in lung and ileum tissues over a specified time period. Within a span of 72 hours, we observed an intense viral transduction induced by the spike protein, which was detected from the central bronchus to the bronchiole and alveolus in the lung (levels 3 to 8). Similarly, we observed the transduction of PSV-S in the villi and crypts of the ileum. Interestingly, our precise three-dimensional colocalization analysis revealed that only 73.74% ± 1.76% of the PSV-S transduction depended on chiACE2. Furthermore, type 2 innate lymphoid cells (ILC2s) exhibited the most pronounced activation in the gut mucosa. This finding indicates the significant role of ILC2s as contributors to the mucosal defense against viral infections. Our data shed light on the critical involvement of ILC2s and their intricate three-dimensional regulatory network in combating SARS-CoV-2 within the mucosa.IMPORTANCEOur study revealed the spatial interaction between humanized ACE2 and pseudovirus expressing Spike, emphasizing the role of type 2 innate lymphoid cells during the initial phase of viral infection. These findings provide a foundation for the development of mucosal vaccines and other treatment approaches for both pre- and post-infection management of coronavirus disease 2019.
Keywords: ILC2; SARS-CoV-2; mucosal immunity; tissue transparency and 3D imaging.