IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v590y2021i7847d10.1038_s41586-020-03148-w.html
   My bibliography  Save this article

Circuits between infected macrophages and T cells in SARS-CoV-2 pneumonia

Author

Listed:
  • Rogan A. Grant

    (Northwestern University)

  • Luisa Morales-Nebreda

    (Northwestern University)

  • Nikolay S. Markov

    (Northwestern University)

  • Suchitra Swaminathan

    (Northwestern University
    Northwestern University)

  • Melissa Querrey

    (Northwestern University)

  • Estefany R. Guzman

    (Northwestern University)

  • Darryl A. Abbott

    (Northwestern University)

  • Helen K. Donnelly

    (Northwestern University)

  • Alvaro Donayre

    (Northwestern University)

  • Isaac A. Goldberg

    (Northwestern University)

  • Zasu M. Klug

    (Northwestern University)

  • Nicole Borkowski

    (Northwestern University)

  • Ziyan Lu

    (Northwestern University)

  • Hermon Kihshen

    (Northwestern University)

  • Yuliya Politanska

    (Northwestern University)

  • Lango Sichizya

    (Northwestern University)

  • Mengjia Kang

    (Northwestern University)

  • Ali Shilatifard

    (Northwestern University
    Northwestern University)

  • Chao Qi

    (Northwestern University)

  • Jon W. Lomasney

    (Northwestern University)

  • A. Christine Argento

    (Northwestern University)

  • Jacqueline M. Kruser

    (Northwestern University)

  • Elizabeth S. Malsin

    (Northwestern University)

  • Chiagozie O. Pickens

    (Northwestern University)

  • Sean B. Smith

    (Northwestern University)

  • James M. Walter

    (Northwestern University)

  • Anna E. Pawlowski

    (Northwestern University)

  • Daniel Schneider

    (Northwestern University)

  • Prasanth Nannapaneni

    (Northwestern University)

  • Hiam Abdala-Valencia

    (Northwestern University)

  • Ankit Bharat

    (Northwestern University
    Northwestern University)

  • Cara J. Gottardi

    (Northwestern University)

  • G. R. Scott Budinger

    (Northwestern University)

  • Alexander V. Misharin

    (Northwestern University
    Northwestern University)

  • Benjamin D. Singer

    (Northwestern University
    Northwestern University
    Northwestern University)

  • Richard G. Wunderink

    (Northwestern University
    Northwestern University)

Abstract

Some patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop severe pneumonia and acute respiratory distress syndrome1 (ARDS). Distinct clinical features in these patients have led to speculation that the immune response to virus in the SARS-CoV-2-infected alveolus differs from that in other types of pneumonia2. Here we investigate SARS-CoV-2 pathobiology by characterizing the immune response in the alveoli of patients infected with the virus. We collected bronchoalveolar lavage fluid samples from 88 patients with SARS-CoV-2-induced respiratory failure and 211 patients with known or suspected pneumonia from other pathogens, and analysed them using flow cytometry and bulk transcriptomic profiling. We performed single-cell RNA sequencing on 10 bronchoalveolar lavage fluid samples collected from patients with severe coronavirus disease 2019 (COVID-19) within 48 h of intubation. In the majority of patients with SARS-CoV-2 infection, the alveolar space was persistently enriched in T cells and monocytes. Bulk and single-cell transcriptomic profiling suggested that SARS-CoV-2 infects alveolar macrophages, which in turn respond by producing T cell chemoattractants. These T cells produce interferon-γ to induce inflammatory cytokine release from alveolar macrophages and further promote T cell activation. Collectively, our results suggest that SARS-CoV-2 causes a slowly unfolding, spatially limited alveolitis in which alveolar macrophages containing SARS-CoV-2 and T cells form a positive feedback loop that drives persistent alveolar inflammation.

Suggested Citation

  • Rogan A. Grant & Luisa Morales-Nebreda & Nikolay S. Markov & Suchitra Swaminathan & Melissa Querrey & Estefany R. Guzman & Darryl A. Abbott & Helen K. Donnelly & Alvaro Donayre & Isaac A. Goldberg & Z, 2021. "Circuits between infected macrophages and T cells in SARS-CoV-2 pneumonia," Nature, Nature, vol. 590(7847), pages 635-641, February.
  • Handle: RePEc:nat:nature:v:590:y:2021:i:7847:d:10.1038_s41586-020-03148-w
    DOI: 10.1038/s41586-020-03148-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-020-03148-w
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/s41586-020-03148-w?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Rhys Hamon & Miranda P. Ween, 2022. "E-Cigarette Vapour Increases ACE2 and TMPRSS2 Expression in a Flavour- and Nicotine-Dependent Manner," IJERPH, MDPI, vol. 19(22), pages 1-12, November.
    2. Hong Lei & Aqu Alu & Jingyun Yang & Xi He & Cai He & Wenyan Ren & Zimin Chen & Weiqi Hong & Li Chen & Xuemei He & Li Yang & Jiong Li & Zhenling Wang & Wei Wang & Yuquan Wei & Shuaiyao Lu & Guangwen Lu, 2023. "Cationic crosslinked carbon dots-adjuvanted intranasal vaccine induces protective immunity against Omicron-included SARS-CoV-2 variants," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    3. Learta Pervizaj-Oruqaj & Balachandar Selvakumar & Maximiliano Ruben Ferrero & Monika Heiner & Christina Malainou & Rolf David Glaser & Jochen Wilhelm & Marek Bartkuhn & Astrid Weiss & Ioannis Alexopou, 2024. "Alveolar macrophage-expressed Plet1 is a driver of lung epithelial repair after viral pneumonia," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    4. Aloysious Ssemaganda & Huong Mai Nguyen & Faisal Nuhu & Naima Jahan & Catherine M. Card & Sandra Kiazyk & Giulia Severini & Yoav Keynan & Ruey-Chyi Su & Hezhao Ji & Bernard Abrenica & Paul J. McLaren , 2022. "Expansion of cytotoxic tissue-resident CD8+ T cells and CCR6+CD161+ CD4+ T cells in the nasal mucosa following mRNA COVID-19 vaccination," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    5. Erick Armingol & Hratch M. Baghdassarian & Cameron Martino & Araceli Perez-Lopez & Caitlin Aamodt & Rob Knight & Nathan E. Lewis, 2022. "Context-aware deconvolution of cell–cell communication with Tensor-cell2cell," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    6. Eric D. Morrell & Sarah E. Holton & Matthew Lawrance & Marika Orlov & Zoie Franklin & Mallorie A. Mitchem & Hannah DeBerg & Vivian H. Gersuk & Ashley Garay & Elizabeth Barnes & Ted Liu & Ithan D. Pelt, 2023. "The transcriptional and phenotypic characteristics that define alveolar macrophage subsets in acute hypoxemic respiratory failure," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    7. Andrea Toth & Paranthaman Kannan & John Snowball & Matthew Kofron & Joseph A. Wayman & James P. Bridges & Emily R. Miraldi & Daniel Swarr & William J. Zacharias, 2023. "Alveolar epithelial progenitor cells require Nkx2-1 to maintain progenitor-specific epigenomic state during lung homeostasis and regeneration," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    8. Rachel Erickson & Chang Huang & Cameron Allen & Joanna Ireland & Gwynne Roth & Zhongcheng Zou & Jinghua Lu & Bernard A. P. Lafont & Nicole L. Garza & Beniah Brumbaugh & Ming Zhao & Motoshi Suzuki & Li, 2023. "SARS-CoV-2 infection of human lung epithelial cells induces TMPRSS-mediated acute fibrin deposition," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    9. Xiaolei Pei & Li Liu & Jieru Wang & Changyuan Guo & Qingqing Li & Jia Li & Qian Ren & Runzhi Ma & Yi Zheng & Yan Zhang & Li Liu & Danfeng Zheng & Pingzhang Wang & Ping Jiang & Xiaoming Feng & Erlie Ji, 2024. "Exosomal secreted SCIMP regulates communication between macrophages and neutrophils in pneumonia," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:590:y:2021:i:7847:d:10.1038_s41586-020-03148-w. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.