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Airway epithelial CD47 plays a critical role in inducing influenza virus-mediated bacterial super-infection

Author

Listed:
  • Sungmin Moon

    (Yonsei University College of Medicine
    Yonsei University College of Medicine)

  • Seunghan Han

    (Yonsei University College of Medicine
    Yonsei University College of Medicine)

  • In-Hwan Jang

    (Seoul National University)

  • Jaechan Ryu

    (Institut Pasteur)

  • Min-Seok Rha

    (Yonsei University College of Medicine)

  • Hyung-Ju Cho

    (Yonsei University College of Medicine
    Yonsei University College of Medicine)

  • Sang Sun Yoon

    (Yonsei University College of Medicine)

  • Ki Taek Nam

    (Yonsei University College of Medicine)

  • Chang-Hoon Kim

    (Yonsei University College of Medicine
    Yonsei University College of Medicine)

  • Man-Seong Park

    (Korea University College of Medicine)

  • Je Kyung Seong

    (Seoul National University
    Seoul National University)

  • Won-Jae Lee

    (Seoul National University)

  • Joo-Heon Yoon

    (Yonsei University College of Medicine
    Yonsei University College of Medicine)

  • Youn Wook Chung

    (Yonsei University College of Medicine
    Yonsei University College of Medicine)

  • Ji-Hwan Ryu

    (Yonsei University College of Medicine
    Yonsei University College of Medicine)

Abstract

Respiratory viral infection increases host susceptibility to secondary bacterial infections, yet the precise dynamics within airway epithelia remain elusive. Here, we elucidate the pivotal role of CD47 in the airway epithelium during bacterial super-infection. We demonstrated that upon influenza virus infection, CD47 expression was upregulated and localized on the apical surface of ciliated cells within primary human nasal or bronchial epithelial cells. This induced CD47 exposure provided attachment sites for Staphylococcus aureus, thereby compromising the epithelial barrier integrity. Through bacterial adhesion assays and in vitro pull-down assays, we identified fibronectin-binding proteins (FnBP) of S. aureus as a key component that binds to CD47. Furthermore, we found that ciliated cell-specific CD47 deficiency or neutralizing antibody-mediated CD47 inactivation enhanced in vivo survival rates. These findings suggest that interfering with the interaction between airway epithelial CD47 and pathogenic bacterial FnBP holds promise for alleviating the adverse effects of super-infection.

Suggested Citation

  • Sungmin Moon & Seunghan Han & In-Hwan Jang & Jaechan Ryu & Min-Seok Rha & Hyung-Ju Cho & Sang Sun Yoon & Ki Taek Nam & Chang-Hoon Kim & Man-Seong Park & Je Kyung Seong & Won-Jae Lee & Joo-Heon Yoon & , 2024. "Airway epithelial CD47 plays a critical role in inducing influenza virus-mediated bacterial super-infection," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47963-5
    DOI: 10.1038/s41467-024-47963-5
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    References listed on IDEAS

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    1. Michelle Reed & Anny-Claude Luissint & Veronica Azcutia & Shuling Fan & Monique N. O’Leary & Miguel Quiros & Jennifer Brazil & Asma Nusrat & Charles A. Parkos, 2019. "Epithelial CD47 is critical for mucosal repair in the murine intestine in vivo," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    2. Denisa Bojkova & Kevin Klann & Benjamin Koch & Marek Widera & David Krause & Sandra Ciesek & Jindrich Cinatl & Christian Münch, 2020. "Proteomics of SARS-CoV-2-infected host cells reveals therapy targets," Nature, Nature, vol. 583(7816), pages 469-472, July.
    3. Rémy Robinot & Mathieu Hubert & Guilherme Dias Melo & Françoise Lazarini & Timothée Bruel & Nikaïa Smith & Sylvain Levallois & Florence Larrous & Julien Fernandes & Stacy Gellenoncourt & Stéphane Riga, 2021. "SARS-CoV-2 infection induces the dedifferentiation of multiciliated cells and impairs mucociliary clearance," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
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