title: Interferon-α and interleukin-12 are induced, respectively, by double-stranded DNA and single-stranded RNA in human myeloid dendritic cells.
abstract: Dendritic cells (DCs) are initiators of innate immunity and acquired immunity as cells linking these two bio-defence systems through the production of cytokines such as interferon-α (IFN-α) and interleukin-12 (IL-12). Nucleic acids such as DNA from damaged cells or pathogens are important activators not only for anti-microbial innate immune responses but also in the pathogenesis of IFN-related autoimmune diseases. Plasmacytoid DCs are regarded as the main effectors for the DNA-mediated innate immunity by possessing DNA-sensing toll-like receptor 9 (TLR9). We here found that double-stranded DNA (dsDNA) complexed with lipotransfectants triggered activation of human monocyte-derived DCs (moDCs), leading to the preferential production of IFN-α but not IL-12. This indicates that myeloid DCs also function as supportive effectors against the invasion of pathogenic microbes through the DNA-mediated activation in innate immunity. The dsDNA with lipotransfectants can be taken up by moDCs without co-localization of endosomal LAMP1 staining, and the dsDNA-mediated IFN-α production was not impaired by chloroquine. These findings indicate that moDC activation by dsDNA does not involve the endosomal TLR pathway. In contrast, single-stranded RNA (ssRNA) stimulated moDCs to secrete IL-12 but not IFN-α. This process was inhibited by chloroquine, suggesting an involvement of the TLR pathway in ssRNA-mediated moDC activation. As might be inferred from our findings, myeloid DCs may function as a traffic control between innate immunity via IFN-α production and acquired immunity via IL-12 production, depending on the type of nucleic acids. Our results provide a new insight into the biological action of myeloid DCs underlying the DNA-mediated activation of protective or pathogenic immunity.
authors.affiliation: First Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Katashiba
authors.forename: Rie
authors.initials: R
authors.lastname: Miyamoto
authors.forename: Akira
authors.initials: A
authors.lastname: Hyo
authors.forename: Keiko
authors.initials: K
authors.lastname: Shimamoto
authors.forename: Naoko
authors.initials: N
authors.lastname: Murakami
authors.forename: Makoto
authors.initials: M
authors.lastname: Ogata
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Amakawa
authors.forename: Muneo
authors.initials: M
authors.lastname: Inaba
authors.forename: Shosaku
authors.initials: S
authors.lastname: Nomura
authors.forename: Shirou
authors.initials: S
authors.lastname: Fukuhara
authors.forename: Tomoki
authors.initials: T
authors.lastname: Ito
mesh_terms: D004247:DNA / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D016898:Interferon-alpha / Q000276:immunology / Q000378:metabolism*; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D012313:RNA / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000378:metabolism
chemical_list: D016898:Interferon-alpha; D051217:Toll-Like Receptor 9; D018664:Interleukin-12; D012313:RNA; D004247:DNA