Duox2-induced innate immune responses in the respiratory epithelium and intranasal delivery of Duox2 DNA using polymer that mediates immunization
Respiratory mucosa especially nasal epithelium is well known as the first-line barrier of air-borne pathogens. High levels of reactive oxygen species (ROS) are detected in in vitro cultured human epithelial cells and in vivo lung. With identification of NADPH oxidase (Nox) system of respiratory epithelium, the antimicrobial role of ROS has been studied. Duox2 is the most abundant Nox isoform and produces the regulated amount of ROS in respiratory epithelium. Duox2-derived ROS are involved in antiviral innate immune responses but more studies are needed to verify the mechanism. In respiratory epithelium, Duox2-derived ROS is critical for recognition of virus through families retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5) at the early stage of antiviral innate immune responses. Various secreted interferons (IFNs) play essential roles for antiviral host defense by downstream cell signaling, and transcription of IFN-stimulated genes is started to suppress viral replication. Type I and type III IFNs are verified more responsible for influenza A virus (IAV) infection in respiratory epithelium and Duox2 is required to regulate IFN-related immune responses. Transient overexpression of Duox2 using cationic polymer polyethylenimine (PEI) induces secretion of type I and type III IFNs and significantly attenuated IAV replication in respiratory epithelium. Here, we discuss Duox2-mediated antiviral innate immune responses and the role of Duox2 as a mucosal vaccine to resist respiratory viral infection.
KeywordsDuox2 Cationic polymer Reactive oxygen species Influenza A virus Respiratory epithelium
Y.J.J. and H.J.K. conceived the study and designed the experimental plan. Y.J.J. carried out a major portion of the study including data collection and H.J.K. drafted the manuscript.
This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, (2016R1D1A1B01014116) (H.J.K.), a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI15C2923) (H.J.K.), and a grant from the Korea Healthcare Technology R&D Project of the Ministry for Health, Welfare, and Family Affairs (HI15C0694) (H.J.K.).
Compliance with ethical standards
The authors declare that they have no conflict of interest.
This article does not contain any studies with human participants performed by any of the authors. The Institutional Review Board of the Seoul National University College of Medicine approved all experiments (IACUC number 15-0263) and the data collection was carried out in accordance with the approved guidelines.
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