ArticleImmunity2021
SARS-CoV-2 exacerbates proinflammatory responses in myeloid cells through C-type lectin receptors and Tweety family member 2.
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Article in Immunity, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 1 of them a synthesis that pooled it.
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114citing papers in PubMed, 1 pooled it
9.5field-weighted citation impact, top 2% of its field
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Who cites it
114 citing papers in PubMed, 1 synthesis or guideline pooled it, 168 citations in OpenAlex.
- Outlook of therapeutic and diagnostic competency of nanobodies against SARS-CoV-2: A systematic review.Analytical biochemistry · 2022Pooled it
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- Longitudinal analysis reveals myeloid cell contributions to murine neuroPASC pathogenesis.Nature communications · 2026Article
- Covalent Activation of the C-type Lectin DC-SIGN.Angewandte Chemie (International ed. in English) · 2026Article
- Immunoregulatory effect of metformin in monocytes exposed to SARS-CoV-2 spike protein subunit 1.Immunometabolism (Cobham, Surrey) · 2026Article
- Cell type-specific eQTL analysis of COVID-19 based on single-cell transcriptomic data.NAR genomics and bioinformatics · 2025Article
- Anti-SARS-CoV-2 antibodies from severe COVID-19 individuals or S2 immunizations do not worsen disease in hamsters.Communications biology · 2025Article
- P selectin promotes SARS-CoV-2 interactions with platelets and the endothelium.The Journal of clinical investigation · 2025Article
- Comprehensive mapping of the signaling events evoked by SARS-CoV-2 variants delta and omicron in human astrocytes.Scientific reports · 2025Article
- Engineered Dual-Function Antibody-Like Proteins to Combat SARS-CoV-2-Induced Immune Dysregulation and Inflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A Vascularized Human Organ Chip Reveals SARS-CoV-2 Susceptibility in Developmentally Guided Tissue Maturation.Cellular and molecular bioengineering · 2025Article
- Immune Responses of Dendritic Cells to Zoonotic DNA and RNA Viruses.Veterinary sciences · 2025Review
- A High-Throughput Cell-Based Luciferase Reporter Assay for Identifying Inhibitors of ASGR1.International journal of molecular sciences · 2025Article
- Advances and applications in single-cell and spatial genomics.Science China. Life sciences · 2025Review
- Monitoring Macrophage Polarization in Infectious Disease, Lesson From SARS-CoV-2 Infection.Reviews in medical virology · 2025Review
- Article
- Asialoglycoprotein receptor 1: a multifaceted receptor in the liver and cardiovascular system.Frontiers in medicine · 2025Review
- Intestinal barrier compromise, viral persistence, and immune dysregulation converge on neurological sequelae in Long COVID.Frontiers in aging neuroscience · 2025Review
- The innate immune response in SARS-CoV2 infection: focus on toll-like receptor 4 in severe disease outcomes.Frontiers in immunology · 2025Review
54 more citing papers are in PubMed but not listed here.
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Authors and funding
50 authors at 8 institutions in 2 countries.
Qiao LuDepartment 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.
Jia LiuDepartment 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.
Shuai ZhaoWestlake 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, Zhejiang Province 310024, China; Institute of Basics Medical Sciences, Westlake Institute for Advanced Study, School of Life Sciences, Westlake University, Hangzhou, Zhejiang Province 310024, China.
Maria Florencia Gomez CastroDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Maudry Laurent-RolleDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA.
Jianbo DongAb Studio, Inc., Hayward, CA 94545, USA.
Xiaojuan RanWestlake 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, Zhejiang Province 310024, China; Institute of Basics Medical Sciences, Westlake Institute for Advanced Study, School of Life Sciences, Westlake University, Hangzhou, Zhejiang Province 310024, China.
Payal Damani-YokotaDepartment of Microbiology, New York University Grossman School of Medicine, New York, NY 10016, USA.
Hongzhen TangWestlake 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, Zhejiang Province 310024, China; Institute of Basics Medical Sciences, Westlake Institute for Advanced Study, School of Life Sciences, Westlake University, Hangzhou, Zhejiang Province 310024, China.
Triantafyllia KarakousiDepartment 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.
Juhee SonDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Maria E KaczmarekDepartment of Microbiology, New York University Grossman School of Medicine, New York, NY 10016, USA.
Ze ZhangDepartment 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.
Stephen T YeungDepartment of Microbiology, New York University Grossman School of Medicine, New York, NY 10016, USA.
Broc T McCuneDepartment 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.
Rita E ChenDepartment 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.
Fei TangBIOPIC, Beijing Advanced Innovation Center for Genomics, School of Life Sciences, Peking University, Beijing 100871, China.
Xianwen RenBIOPIC, Beijing Advanced Innovation Center for Genomics, School of Life Sciences, Peking University, Beijing 100871, China.
Xufeng ChenDepartment of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA.
Jack C C HsuDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA.
Marianna TeplovaDepartment 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.
Betty HuangAb Studio, Inc., Hayward, CA 94545, USA.
Haijing DengWestlake 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, Zhejiang Province 310024, China; Institute of Basics Medical Sciences, Westlake Institute for Advanced Study, School of Life Sciences, Westlake University, Hangzhou, Zhejiang Province 310024, China.
Zhilin LongWestlake 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, Zhejiang Province 310024, China; Institute of Basics Medical Sciences, Westlake Institute for Advanced Study, School of Life Sciences, Westlake University, Hangzhou, Zhejiang Province 310024, China.
Tenny MudiantoDepartment of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA.
Shumin JinWestlake 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, Zhejiang Province 310024, China; Institute of Basics Medical Sciences, Westlake Institute for Advanced Study, School of Life Sciences, Westlake University, Hangzhou, Zhejiang Province 310024, China.
Peng LinWestlake 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, Zhejiang Province 310024, China; Institute of Basics Medical Sciences, Westlake Institute for Advanced Study, School of Life Sciences, Westlake University, Hangzhou, Zhejiang Province 310024, China.
Jasper DuDepartment of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA.
Ruochen ZangDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Tina Tianjiao SuDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA.
Alberto HerreraDepartment of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA.
Ming ZhouWestlake 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, Zhejiang Province 310024, China; Institute of Basics Medical Sciences, Westlake Institute for Advanced Study, School of Life Sciences, Westlake University, Hangzhou, Zhejiang Province 310024, China.
Renhong YanJoint 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, Zhejiang Province 310024, China.
Jia CuiKactus Biosystems Co., Ltd., Shanghai 201114, China.
James ZhuQuantitative Biomedical Research Center, Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Qiang ZhouJoint 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, Zhejiang Province 310024, China.
Tao WangQuantitative Biomedical Research Center, Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Jianzhu MaDepartment of Computer Science, Purdue University, West Lafayette, IN 47907, USA.
Sergei B KoralovDepartment of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA.
Zemin ZhangBIOPIC, Beijing Advanced Innovation Center for Genomics, School of Life Sciences, Peking University, Beijing 100871, China.
Iannis AifantisDepartment of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA.
Leopoldo N SegalDivision of Pulmonary and Critical Care Medicine, New York University School of Medicine, New York, NY 10016, USA.
Michael S DiamondDepartment 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 School of Medicine, St. Louis, MO 63110, USA.
Kamal M KhannaThe 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.
Kenneth A StaplefordDepartment of Microbiology, New York University Grossman School of Medicine, New York, NY 10016, USA.
Peter CresswellDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA.
Yue LiuAb Studio, Inc., Hayward, CA 94545, USA.
Siyuan DingDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: siyuan.ding@wustl.edu.
Qi XieWestlake 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, Zhejiang Province 310024, China; Institute of Basics Medical Sciences, Westlake Institute for Advanced Study, School of Life Sciences, Westlake University, Hangzhou, Zhejiang Province 310024, China. Electronic address: xieqi@westlake.edu.cn.
Jun WangDepartment 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.
New York University · USWestlake University · CNWashington University in St. Louis · USNYU Langone Health · USPeking University · CNYale University · USThe University of Texas Southwestern Medical Center · USPurdue University West Lafayette · US
Funding
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9MWashington University DDRCC Supplemental Equipment RequestP30DK052574 · NIDDK · WASHINGTON UNIVERSITY · PI Nicholas O. Davidson · 2000 to 2026
$30.8MTRAINING IN THE PATHOGENESIS OF INFECTIOUS DISEASEST32AI007517 · NIAID · YALE UNIVERSITY · PI Jaimie Meyer, Albert C Shaw · 1997 to 2026
$6.1MHuman antibody-based countermeasures against the Wuhan Coronavirus SARS-CoV-2R01AI157155 · NIAID · WASHINGTON UNIVERSITY · PI BARIC, RALPH S, CROWE, JAMES E · 2020 to 2024
$6.0MMolecular Aspects of Human CD1d FunctionsR01AI059167 · NIAID · YALE UNIVERSITY · PI CRESSWELL, PETER · 2004 to 2019
$5.6MNovel lung resident interstitial macrophage subset with distinct localization and polarizationR01AI143861 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI KHANNA, KAMAL MOHAN · 2019 to 2023
$3.3MTargeting an RNA Binding Protein Network in Acute Myeloid LeukemiaR01CA242020 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI ABDEL-WAHAB, OMAR, AIFANTIS, IANNIS · 2020 to 2024
$2.7MThe cohesin complex as a tumor suppressor in myeloid leukemiaR01CA216421 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI AIFANTIS, IANNIS, LEVINE, ROSS L · 2017 to 2021
$2.5MMechanisms of enhancer regulation in leukemiaR01CA228135 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI AIFANTIS, IANNIS · 2019 to 2023
$2.5MMapping cancer micro-environments for acute leukemiaR01CA202025 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI AIFANTIS, IANNIS, SCHWAB, SUSAN RUTH · 2016 to 2020
$2.3MPost-translational control of cancer cell stress response and metastasisR01CA202027 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI AIFANTIS, IANNIS, HERNANDO, EVA · 2016 to 2020
$2.3MInterferon-Stimulated Gene Inhibition of Rotavirus Replication and Viral AntagonismR01AI150796 · NIAID · WASHINGTON UNIVERSITY · PI DING, SIYUAN · 2020 to 2024
$2.0MNCATS NIH HHS UL1 TR001863NCI NIH HHS R01 CA202025NCI NIH HHS R01 CA202027NCI NIH HHS R01 CA228135NCI NIH HHS R01 CA242020NIAID NIH HHS R00 AI135031NIAID NIH HHS R01 AI059167NIAID NIH HHS R01 AI143861NIAID NIH HHS R01 AI150796NIAID NIH HHS R01 AI157155NIAID NIH HHS R21 AI163924NIAID NIH HHS T32 AI007517NIDDK NIH HHS P30 DK052574
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.
Indexed as
Host-Pathogen InteractionsAngiotensin-Converting Enzyme 2Binding SitesCell LineCOVID-19CytokinesGene Expression RegulationHumansInflammation MediatorsLectins, C-TypeMembrane ProteinsModels, MolecularMyeloid CellsNeoplasm ProteinsProtein BindingProtein ConformationAngiotensin-Converting Enzyme 2CytokinesInflammation MediatorsLectins, C-TypeMembrane ProteinsNeoplasm ProteinsSingle-Domain AntibodiesSpike Glycoprotein, CoronavirusTTYH2 protein, humanASGR1CLEC10ACOVID-19DC-SIGNLSECtinL-SIGNmyeloid cellsproinflammatory responsesSARS-CoV-2TTYH2
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