title: Retinoic acid-inducible gene-I-like receptor (RLR)-mediated antiviral innate immune responses in the lower respiratory tract: Roles of TRAF3 and TRAF5.
abstract: Upon viral infection, the cytoplasmic viral sensor retinoic acid-inducible gene-I (RIG-I) recognizes viral RNA to activate antiviral signaling to induce type I interferon (IFN). RIG-I-like receptors (RLRs) activate antiviral signaling in a tissue-specific manner. The molecular mechanism underlying antiviral signaling in the respiratory system remains unclear. We studied antiviral signaling in the lower respiratory tract (LRT), which is the site of many harmful viral infections. Epithelial cells of the LRT can be roughly divided into two groups: bronchial epithelial cells (BECs) and pulmonary alveolar epithelial cells (AECs). These two cell types exhibit different phenotypes; therefore, we hypothesized that these cells may play different roles in antiviral innate immunity. We found that BECs exhibited higher antiviral activity than AECs. TNF receptor-associated factor 3 (TRAF3) has been shown to be a crucial molecule in RLR signaling. The expression levels of TRAF3 and TRAF5, which have conserved domains that are nearly identical, in the LRT were examined. We found that the bronchus exhibited the highest expression levels of TRAF3 and TRAF5 in the LRT. These findings suggest the importance of the bronchus in antiviral innate immunity in the LRT and indicate that TRAF3 and TRAF5 may contribute to RLR signaling.
authors.affiliation: Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Chiba
authors.affiliation: Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. Electronic address: tomo1027@hirosaki-u.ac.jp.
authors.forename: Tomoh
authors.initials: T
authors.lastname: Matsumiya
authors.affiliation: Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Tsugumi
authors.initials: T
authors.lastname: Satoh
authors.affiliation: Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Hayakari
authors.affiliation: Department of Dentistry and Oral Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Furudate
authors.affiliation: Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Fei
authors.initials: F
authors.lastname: Xing
authors.affiliation: Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Yoshida
authors.affiliation: Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Tanji
authors.affiliation: Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Mizukami
authors.affiliation: Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Tadaatsu
authors.initials: T
authors.lastname: Imaizumi
authors.affiliation: Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Etsuro
authors.initials: E
authors.lastname: Ito
mesh_terms: D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000276:immunology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D004947:Esophagus / Q000737:chemistry / Q000187:drug effects / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D016899:Interferon-beta / Q000096:biosynthesis / Q000276:immunology; D007830:Larynx / Q000737:chemistry / Q000187:drug effects / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000187:drug effects / Q000276:immunology; D009928:Organ Specificity; D011070:Poly I-C / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D011971:Receptors, Immunologic; D015398:Signal Transduction; D048008:TNF Receptor-Associated Factor 3 / Q000235:genetics* / Q000276:immunology; D048015:TNF Receptor-Associated Factor 5 / Q000235:genetics* / Q000276:immunology
chemical_list: D011971:Receptors, Immunologic; D048008:TNF Receptor-Associated Factor 3; D048015:TNF Receptor-Associated Factor 5; C090656:TRAF3 protein, human; D016899:Interferon-beta; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D011070:Poly I-C
keywords: Antiviral signaling; Lower respiratory tract; RLRs; TRAF3; TRAF5