Interferon-α and interleukin-12 are induced, respectively, by double-stranded DNA and single-stranded RNA in human myeloid dendritic cells.
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.
Katashiba
Yuichi
Y
First Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
Miyamoto
Rie
R
Hyo
Akira
A
Shimamoto
Keiko
K
Murakami
Naoko
N
Ogata
Makoto
M
Amakawa
Ryuichi
R
Inaba
Muneo
M
Nomura
Shosaku
S
Fukuhara
Shirou
S
Ito
Tomoki
T
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
D016898:Interferon-alpha; D051217:Toll-Like Receptor 9; D018664:Interleukin-12; D012313:RNA; D004247:DNA