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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
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    Citations

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    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. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    9. 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.

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