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SARS-CoV-2 exacerbates proinflammatory responses in myeloid cells through C-type lectin receptors and Tweety family member 2.
Lu, Qiao; Liu, Jia; Zhao, Shuai; Gomez Castro, Maria Florencia; Laurent-Rolle, Maudry; Dong, Jianbo; Ran, Xiaojuan; Damani-Yokota, Payal; Tang, Hongzhen; Karakousi, Triantafyllia; Son, Juhee; Kaczmarek, Maria E; Zhang, Ze; Yeung, Stephen T; McCune, Broc T; Chen, Rita E; Tang, Fei; Ren, Xianwen; Chen, Xufeng; Hsu, Jack C C; Teplova, Marianna; Huang, Betty; Deng, Haijing; Long, Zhilin; Mudianto, Tenny; Jin, Shumin; Lin, Peng; Du, Jasper; Zang, Ruochen; Su, Tina Tianjiao; Herrera, Alberto; Zhou, Ming; Yan, Renhong; Cui, Jia; Zhu, James; Zhou, Qiang; Wang, Tao; Ma, Jianzhu; Koralov, Sergei B; Zhang, Zemin; Aifantis, Iannis; Segal, Leopoldo N; Diamond, Michael S; Khanna, Kamal M; Stapleford, Kenneth A; Cresswell, Peter; Liu, Yue; Ding, Siyuan; Xie, Qi; Wang, Jun.
  • Lu Q; Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA; The Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, NY 10016, USA.
  • Liu J; Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA; The Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, NY 10016, USA.
  • Zhao S; Westlake Laboratory of Life Sciences and Biomedicine, Center for Infectious Diseases Research, Zhejiang Provincial Laboratory of Life Sciences and Biomedicine, Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou,
  • Gomez Castro MF; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Laurent-Rolle M; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA.
  • Dong J; Ab Studio, Inc., Hayward, CA 94545, USA.
  • Ran X; Westlake Laboratory of Life Sciences and Biomedicine, Center for Infectious Diseases Research, Zhejiang Provincial Laboratory of Life Sciences and Biomedicine, Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou,
  • Damani-Yokota P; Department of Microbiology, New York University Grossman School of Medicine, New York, NY 10016, USA.
  • Tang H; Westlake Laboratory of Life Sciences and Biomedicine, Center for Infectious Diseases Research, Zhejiang Provincial Laboratory of Life Sciences and Biomedicine, Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou,
  • Karakousi T; Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA; The Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, NY 10016, USA.
  • Son J; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Kaczmarek ME; Department of Microbiology, New York University Grossman School of Medicine, New York, NY 10016, USA.
  • Zhang Z; Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA; The Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, NY 10016, USA.
  • Yeung ST; Department of Microbiology, New York University Grossman School of Medicine, New York, NY 10016, USA.
  • McCune BT; Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Chen RE; Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Tang F; BIOPIC, Beijing Advanced Innovation Center for Genomics, School of Life Sciences, Peking University, Beijing 100871, China.
  • Ren X; BIOPIC, Beijing Advanced Innovation Center for Genomics, School of Life Sciences, Peking University, Beijing 100871, China.
  • Chen X; Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA.
  • Hsu JCC; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA.
  • Teplova M; Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA; The Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, NY 10016, USA.
  • Huang B; Ab Studio, Inc., Hayward, CA 94545, USA.
  • Deng H; Westlake Laboratory of Life Sciences and Biomedicine, Center for Infectious Diseases Research, Zhejiang Provincial Laboratory of Life Sciences and Biomedicine, Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou,
  • Long Z; Westlake Laboratory of Life Sciences and Biomedicine, Center for Infectious Diseases Research, Zhejiang Provincial Laboratory of Life Sciences and Biomedicine, Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou,
  • Mudianto T; Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA.
  • Jin S; Westlake Laboratory of Life Sciences and Biomedicine, Center for Infectious Diseases Research, Zhejiang Provincial Laboratory of Life Sciences and Biomedicine, Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou,
  • Lin P; Westlake Laboratory of Life Sciences and Biomedicine, Center for Infectious Diseases Research, Zhejiang Provincial Laboratory of Life Sciences and Biomedicine, Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou,
  • Du J; Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA.
  • Zang R; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Su TT; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA.
  • Herrera A; Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA.
  • Zhou M; Westlake Laboratory of Life Sciences and Biomedicine, Center for Infectious Diseases Research, Zhejiang Provincial Laboratory of Life Sciences and Biomedicine, Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou,
  • Yan R; Joint Research Center of Hangzhou First Hospital Group and Westlake University, Center for Infectious Diseases Research, Zhejiang Provincial Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou,
  • Cui J; Kactus Biosystems Co., Ltd., Shanghai 201114, China.
  • Zhu J; Quantitative Biomedical Research Center, Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Zhou Q; Joint Research Center of Hangzhou First Hospital Group and Westlake University, Center for Infectious Diseases Research, Zhejiang Provincial Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou,
  • Wang T; Quantitative Biomedical Research Center, Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Ma J; Department of Computer Science, Purdue University, West Lafayette, IN 47907, USA.
  • Koralov SB; Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA.
  • Zhang Z; BIOPIC, Beijing Advanced Innovation Center for Genomics, School of Life Sciences, Peking University, Beijing 100871, China.
  • Aifantis I; Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA.
  • Segal LN; Division of Pulmonary and Critical Care Medicine, New York University School of Medicine, New York, NY 10016, USA.
  • Diamond MS; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University Schoo
  • Khanna KM; The Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, NY 10016, USA; Department of Microbiology, New York University Grossman School of Medicine, New York, NY 10016, USA.
  • Stapleford KA; Department of Microbiology, New York University Grossman School of Medicine, New York, NY 10016, USA.
  • Cresswell P; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA.
  • Liu Y; Ab Studio, Inc., Hayward, CA 94545, USA.
  • Ding S; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: siyuan.ding@wustl.edu.
  • Xie Q; Westlake Laboratory of Life Sciences and Biomedicine, Center for Infectious Diseases Research, Zhejiang Provincial Laboratory of Life Sciences and Biomedicine, Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou,
  • Wang J; Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA; The Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, NY 10016, USA. Electronic address: jun.wang@nyulangone.org.
Immunity ; 54(6): 1304-1319.e9, 2021 06 08.
Article in English | MEDLINE | ID: covidwho-1246001
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Myeloid Cells / Lectins, C-Type / Host-Pathogen Interactions / SARS-CoV-2 / COVID-19 / Membrane Proteins / Neoplasm Proteins Type of study: Prognostic study Limits: Humans Language: English Journal: Immunity Journal subject: Allergy and Immunology Year: 2021 Document Type: Article Affiliation country: J.immuni.2021.05.006

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Myeloid Cells / Lectins, C-Type / Host-Pathogen Interactions / SARS-CoV-2 / COVID-19 / Membrane Proteins / Neoplasm Proteins Type of study: Prognostic study Limits: Humans Language: English Journal: Immunity Journal subject: Allergy and Immunology Year: 2021 Document Type: Article Affiliation country: J.immuni.2021.05.006