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

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, Youn Wook Chung () and Ji-Hwan Ryu ()
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Sungmin Moon: Yonsei University College of Medicine
Seunghan Han: 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
Sang Sun Yoon: Yonsei University College of Medicine
Ki Taek Nam: Yonsei University College of Medicine
Chang-Hoon Kim: Yonsei University College of Medicine
Man-Seong Park: Korea University College of Medicine
Je Kyung Seong: Seoul National University
Won-Jae Lee: Seoul National University
Joo-Heon Yoon: Yonsei University College of Medicine
Youn Wook Chung: Yonsei University College of Medicine
Ji-Hwan Ryu: Yonsei University College of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-47963-5

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