PMID- 20875078
OWN - NLM
STAT- MEDLINE
DCOM- 20110215
LR  - 20211020
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Print)
IS  - 0019-2805 (Linking)
VI  - 132
IP  - 2
DP  - 2011 Feb
TI  - Interferon-alpha and interleukin-12 are induced, respectively, by double-stranded DNA 
      and single-stranded RNA in human myeloid dendritic cells.
PG  - 165-73
LID - 10.1111/j.1365-2567.2010.03350.x [doi]
AB  - 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-alpha (IFN-alpha) 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-alpha 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-alpha 
      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-alpha. 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-alpha 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.
FAU - Katashiba, Yuichi
AU  - Katashiba Y
AD  - First Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
FAU - Miyamoto, Rie
AU  - Miyamoto R
FAU - Hyo, Akira
AU  - Hyo A
FAU - Shimamoto, Keiko
AU  - Shimamoto K
FAU - Murakami, Naoko
AU  - Murakami N
FAU - Ogata, Makoto
AU  - Ogata M
FAU - Amakawa, Ryuichi
AU  - Amakawa R
FAU - Inaba, Muneo
AU  - Inaba M
FAU - Nomura, Shosaku
AU  - Nomura S
FAU - Fukuhara, Shirou
AU  - Fukuhara S
FAU - Ito, Tomoki
AU  - Ito T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100928
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (Interferon-alpha)
RN  - 0 (Toll-Like Receptor 9)
RN  - 187348-17-0 (Interleukin-12)
RN  - 63231-63-0 (RNA)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - DNA/*immunology
MH  - Dendritic Cells/cytology/*immunology/metabolism
MH  - Humans
MH  - Immunity, Innate
MH  - Interferon-alpha/immunology/*metabolism
MH  - Interleukin-12/immunology/*metabolism
MH  - Monocytes/cytology/*immunology/metabolism
MH  - RNA/*immunology
MH  - Toll-Like Receptor 9/metabolism
PMC - PMC3050440
EDAT- 2010/09/30 06:00
MHDA- 2011/02/16 06:00
PMCR- 2012/02/01
CRDT- 2010/09/30 06:00
PHST- 2010/09/30 06:00 [entrez]
PHST- 2010/09/30 06:00 [pubmed]
PHST- 2011/02/16 06:00 [medline]
PHST- 2012/02/01 00:00 [pmc-release]
AID - 10.1111/j.1365-2567.2010.03350.x [doi]
PST - ppublish
SO  - Immunology. 2011 Feb;132(2):165-73. doi: 10.1111/j.1365-2567.2010.03350.x. Epub 
      2010 Sep 28.