tetano
Editor, Senior Moderator
Immunity
. 2021 May 9;S1074-7613(21)00212-0.
doi: 10.1016/j.immuni.2021.05.006. Online ahead of print.
SARS-CoV-2 exacerbates proinflammatory responses in myeloid cells through C-type lectin receptors and Tweety family member 2
Qiao Lu[SUP] 1 [/SUP], Jia Liu[SUP] 1 [/SUP], Shuai Zhao[SUP] 2 [/SUP], Maria Florencia Gomez Castro[SUP] 3 [/SUP], Maudry Laurent-Rolle[SUP] 4 [/SUP], Jianbo Dong[SUP] 5 [/SUP], Xiaojuan Ran[SUP] 2 [/SUP], Payal Damani-Yokota[SUP] 6 [/SUP], Hongzhen Tang[SUP] 2 [/SUP], Triantafyllia Karakousi[SUP] 1 [/SUP], Juhee Son[SUP] 3 [/SUP], Maria E Kaczmarek[SUP] 6 [/SUP], Ze Zhang[SUP] 1 [/SUP], Stephen T Yeung[SUP] 6 [/SUP], Broc T McCune[SUP] 7 [/SUP], Rita E Chen[SUP] 7 [/SUP], Fei Tang[SUP] 8 [/SUP], Xianwen Ren[SUP] 8 [/SUP], Xufeng Chen[SUP] 9 [/SUP], Jack C C Hsu[SUP] 4 [/SUP], Marianna Teplova[SUP] 1 [/SUP], Betty Huang[SUP] 5 [/SUP], Haijing Deng[SUP] 2 [/SUP], Zhilin Long[SUP] 2 [/SUP], Tenny Mudianto[SUP] 9 [/SUP], Shumin Jin[SUP] 2 [/SUP], Peng Lin[SUP] 2 [/SUP], Jasper Du[SUP] 9 [/SUP], Ruochen Zang[SUP] 3 [/SUP], Tina Tianjiao Su[SUP] 4 [/SUP], Alberto Herrera[SUP] 9 [/SUP], Ming Zhou[SUP] 2 [/SUP], Renhong Yan[SUP] 10 [/SUP], Jia Cui[SUP] 11 [/SUP], James Zhu[SUP] 12 [/SUP], Qiang Zhou[SUP] 10 [/SUP], Tao Wang[SUP] 12 [/SUP], Jianzhu Ma[SUP] 13 [/SUP], Sergei B Koralov[SUP] 9 [/SUP], Zemin Zhang[SUP] 8 [/SUP], Iannis Aifantis[SUP] 9 [/SUP], Leopoldo N Segal[SUP] 14 [/SUP], Michael S Diamond[SUP] 15 [/SUP], Kamal M Khanna[SUP] 16 [/SUP], Kenneth A Stapleford[SUP] 6 [/SUP], Peter Cresswell[SUP] 4 [/SUP], Yue Liu[SUP] 5 [/SUP], Siyuan Ding[SUP] 17 [/SUP], Qi Xie[SUP] 18 [/SUP], Jun Wang[SUP] 19 [/SUP]
Affiliations
Abstract
Despite mounting evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) engagement with immune cells, most express little, if any, of the canonical receptor of SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2). Here, using a myeloid cell receptor-focused ectopic expression screen, we identified several C-type lectins (DC-SIGN, L-SIGN, LSECtin, ASGR1, and CLEC10A) and Tweety family member 2 (TTYH2) as glycan-dependent binding partners of the SARS-CoV-2 spike. Except for TTYH2, these molecules primarily interacted with spike via regions outside of the receptor-binding domain. Single-cell RNA sequencing analysis of pulmonary cells from individuals with coronavirus disease 2019 (COVID-19) indicated predominant expression of these molecules on myeloid cells. Although these receptors do not support active replication of SARS-CoV-2, their engagement with the virus induced robust proinflammatory responses in myeloid cells that correlated with COVID-19 severity. We also generated a bispecific anti-spike nanobody that not only blocked ACE2-mediated infection but also the myeloid receptor-mediated proinflammatory responses. Our findings suggest that SARS-CoV-2-myeloid receptor interactions promote immune hyperactivation, which represents potential targets for COVID-19 therapy.
Keywords: ASGR1; CLEC10A; COVID-19; DC-SIGN; L-SIGN; LSECtin; SARS-CoV-2; TTYH2; myeloid cells; proinflammatory responses.
. 2021 May 9;S1074-7613(21)00212-0.
doi: 10.1016/j.immuni.2021.05.006. Online ahead of print.
SARS-CoV-2 exacerbates proinflammatory responses in myeloid cells through C-type lectin receptors and Tweety family member 2
Qiao Lu[SUP] 1 [/SUP], Jia Liu[SUP] 1 [/SUP], Shuai Zhao[SUP] 2 [/SUP], Maria Florencia Gomez Castro[SUP] 3 [/SUP], Maudry Laurent-Rolle[SUP] 4 [/SUP], Jianbo Dong[SUP] 5 [/SUP], Xiaojuan Ran[SUP] 2 [/SUP], Payal Damani-Yokota[SUP] 6 [/SUP], Hongzhen Tang[SUP] 2 [/SUP], Triantafyllia Karakousi[SUP] 1 [/SUP], Juhee Son[SUP] 3 [/SUP], Maria E Kaczmarek[SUP] 6 [/SUP], Ze Zhang[SUP] 1 [/SUP], Stephen T Yeung[SUP] 6 [/SUP], Broc T McCune[SUP] 7 [/SUP], Rita E Chen[SUP] 7 [/SUP], Fei Tang[SUP] 8 [/SUP], Xianwen Ren[SUP] 8 [/SUP], Xufeng Chen[SUP] 9 [/SUP], Jack C C Hsu[SUP] 4 [/SUP], Marianna Teplova[SUP] 1 [/SUP], Betty Huang[SUP] 5 [/SUP], Haijing Deng[SUP] 2 [/SUP], Zhilin Long[SUP] 2 [/SUP], Tenny Mudianto[SUP] 9 [/SUP], Shumin Jin[SUP] 2 [/SUP], Peng Lin[SUP] 2 [/SUP], Jasper Du[SUP] 9 [/SUP], Ruochen Zang[SUP] 3 [/SUP], Tina Tianjiao Su[SUP] 4 [/SUP], Alberto Herrera[SUP] 9 [/SUP], Ming Zhou[SUP] 2 [/SUP], Renhong Yan[SUP] 10 [/SUP], Jia Cui[SUP] 11 [/SUP], James Zhu[SUP] 12 [/SUP], Qiang Zhou[SUP] 10 [/SUP], Tao Wang[SUP] 12 [/SUP], Jianzhu Ma[SUP] 13 [/SUP], Sergei B Koralov[SUP] 9 [/SUP], Zemin Zhang[SUP] 8 [/SUP], Iannis Aifantis[SUP] 9 [/SUP], Leopoldo N Segal[SUP] 14 [/SUP], Michael S Diamond[SUP] 15 [/SUP], Kamal M Khanna[SUP] 16 [/SUP], Kenneth A Stapleford[SUP] 6 [/SUP], Peter Cresswell[SUP] 4 [/SUP], Yue Liu[SUP] 5 [/SUP], Siyuan Ding[SUP] 17 [/SUP], Qi Xie[SUP] 18 [/SUP], Jun Wang[SUP] 19 [/SUP]
Affiliations
- PMID: 34048708
- DOI: 10.1016/j.immuni.2021.05.006
Abstract
Despite mounting evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) engagement with immune cells, most express little, if any, of the canonical receptor of SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2). Here, using a myeloid cell receptor-focused ectopic expression screen, we identified several C-type lectins (DC-SIGN, L-SIGN, LSECtin, ASGR1, and CLEC10A) and Tweety family member 2 (TTYH2) as glycan-dependent binding partners of the SARS-CoV-2 spike. Except for TTYH2, these molecules primarily interacted with spike via regions outside of the receptor-binding domain. Single-cell RNA sequencing analysis of pulmonary cells from individuals with coronavirus disease 2019 (COVID-19) indicated predominant expression of these molecules on myeloid cells. Although these receptors do not support active replication of SARS-CoV-2, their engagement with the virus induced robust proinflammatory responses in myeloid cells that correlated with COVID-19 severity. We also generated a bispecific anti-spike nanobody that not only blocked ACE2-mediated infection but also the myeloid receptor-mediated proinflammatory responses. Our findings suggest that SARS-CoV-2-myeloid receptor interactions promote immune hyperactivation, which represents potential targets for COVID-19 therapy.
Keywords: ASGR1; CLEC10A; COVID-19; DC-SIGN; L-SIGN; LSECtin; SARS-CoV-2; TTYH2; myeloid cells; proinflammatory responses.