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A Moonlighting Protein Secreted by a Nasal Microbiome Fortifies the Innate Host Defense Against Bacterial and Viral Infections

  • Gwanghee Kim (Department of Microbiology and Immunology, Yonsei University College of Medicine) ;
  • Yoojin Lee (Department of Microbiology and Immunology, Yonsei University College of Medicine) ;
  • Jin Sun You (Department of Microbiology and Immunology, Yonsei University College of Medicine) ;
  • Wontae Hwang (Department of Microbiology and Immunology, Yonsei University College of Medicine) ;
  • Jeewon Hwang (Department of Microbiology and Immunology, Yonsei University College of Medicine) ;
  • Hwa Young Kim (Department of Microbiology and Immunology, Yonsei University College of Medicine) ;
  • Jieun Kim (Department of Microbiology and Immunology, Yonsei University College of Medicine) ;
  • Ara Jo (Department of Otorhinolaryngology, Seoul National University College of Medicine) ;
  • In ho Park (Department of Microbiology and Immunology, Yonsei University College of Medicine) ;
  • Mohammed Ali (Department of Microbiology and Immunology, Yonsei University College of Medicine) ;
  • Jongsun Kim (Department of Microbiology and Immunology, Yonsei University College of Medicine) ;
  • Jeon-Soo Shin (Department of Microbiology and Immunology, Yonsei University College of Medicine) ;
  • Ho-Keun Kwon (Department of Microbiology and Immunology, Yonsei University College of Medicine) ;
  • Hyun Jik Kim (Department of Otorhinolaryngology, Seoul National University College of Medicine) ;
  • Sang Sun Yoon (Department of Microbiology and Immunology, Yonsei University College of Medicine)
  • Received : 2023.05.02
  • Accepted : 2023.06.19
  • Published : 2023.08.31
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Abstract

Evidence suggests that the human respiratory tract, as with the gastrointestinal tract, has evolved to its current state in association with commensal microbes. However, little is known about how the airway microbiome affects the development of airway immune system. Here, we uncover a previously unidentified mode of interaction between host airway immunity and a unique strain (AIT01) of Staphylococcus epidermidis, a predominant species of the nasal microbiome. Intranasal administration of AIT01 increased the population of neutrophils and monocytes in mouse lungs. The recruitment of these immune cells resulted in the protection of the murine host against infection by Pseudomonas aeruginosa, a pathogenic bacterium. Interestingly, an AIT01-secreted protein identified as GAPDH, a well-known bacterial moonlighting protein, mediated this protective effect. Intranasal delivery of the purified GAPDH conferred significant resistance against other Gram-negative pathogens (Klebsiella pneumoniae and Acinetobacter baumannii) and influenza A virus. Our findings demonstrate the potential of a native nasal microbe and its secretory protein to enhance innate immune defense against airway infections. These results offer a promising preventive measure, particularly relevant in the context of global pandemics.

Keywords

Acknowledgement

This work was supported by grants from the National Research Foundation of Korea (NRF) grant funded by the Korean Government (2022R1A2C1091845 and 2022M3A9F3017506). This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2022R1A2C2011867 and awarded to HJK). This research was also supported by a grant from the Korean Health Technology Research and Development Project through the Korean Health Industry Development Institute, funded by the Ministry of Health and Welfare of the Republic of Korea (HI23C0795 awarded to HJK). This research was supported by the National Research Foundation of Korea (NRF-2022M3A9I2017587).

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