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Single cell transcriptomics identifies distinct profiles in pediatric acute respiratory distress syndrome

Author

Listed:
  • Tim Flerlage

    (St. Jude Children’s Research Hospital
    University of Tennessee Health Science Center)

  • Jeremy Chase Crawford

    (St. Jude Children’s Research Hospital)

  • E. Kaitlynn Allen

    (St. Jude Children’s Research Hospital)

  • Danielle Severns

    (University of Tennessee Health Science Center)

  • Shaoyuan Tan

    (St. Jude Children’s Research Hospital)

  • Sherri Surman

    (St. Jude Children’s Research Hospital)

  • Granger Ridout

    (St. Jude Children’s Research Hospital)

  • Tanya Novak

    (Critical Care, and Pain Medicine, Boston Children’s Hospital
    Harvard Medical School)

  • Adrienne Randolph

    (Critical Care, and Pain Medicine, Boston Children’s Hospital
    Harvard Medical School
    Harvard Medical School)

  • Alina N. West

    (University of Tennessee Health Science Center)

  • Paul G. Thomas

    (St. Jude Children’s Research Hospital)

Abstract

Acute respiratory distress syndrome (ARDS), termed pediatric ARDS (pARDS) in children, is a severe form of acute respiratory failure (ARF). Pathologic immune responses are implicated in pARDS pathogenesis. Here, we present a description of microbial sequencing and single cell gene expression in tracheal aspirates (TAs) obtained longitudinally from infants with ARF. We show reduced interferon stimulated gene (ISG) expression, altered mononuclear phagocyte (MNP) transcriptional programs, and progressive airway neutrophilia associated with unique transcriptional profiles in patients with moderate to severe pARDS compared to those with no or mild pARDS. We additionally show that an innate immune cell product, Folate Receptor 3 (FOLR3), is enriched in moderate or severe pARDS. Our findings demonstrate distinct inflammatory responses in pARDS that are dependent upon etiology and severity and specifically implicate reduced ISG expression, altered macrophage repair-associated transcriptional programs, and accumulation of aged neutrophils in the pathogenesis of moderate to severe pARDS caused by RSV.

Suggested Citation

  • Tim Flerlage & Jeremy Chase Crawford & E. Kaitlynn Allen & Danielle Severns & Shaoyuan Tan & Sherri Surman & Granger Ridout & Tanya Novak & Adrienne Randolph & Alina N. West & Paul G. Thomas, 2023. "Single cell transcriptomics identifies distinct profiles in pediatric acute respiratory distress syndrome," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39593-0
    DOI: 10.1038/s41467-023-39593-0
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    References listed on IDEAS

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    1. Lindsey W. Plasschaert & Rapolas Žilionis & Rayman Choo-Wing & Virginia Savova & Judith Knehr & Guglielmo Roma & Allon M. Klein & Aron B. Jaffe, 2018. "A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte," Nature, Nature, vol. 560(7718), pages 377-381, August.
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    3. Daniel T. Montoro & Adam L. Haber & Moshe Biton & Vladimir Vinarsky & Brian Lin & Susan E. Birket & Feng Yuan & Sijia Chen & Hui Min Leung & Jorge Villoria & Noga Rogel & Grace Burgin & Alexander M. T, 2018. "A revised airway epithelial hierarchy includes CFTR-expressing ionocytes," Nature, Nature, vol. 560(7718), pages 319-324, August.
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