Immunoadjuvant effects of polyadenylic:polyuridylic acids through TLR3 and TLR7

Double-stranded RNA (dsRNA) is produced upon viral infection and can activate innate immunity. Polyinosinic:polycytidylic acids [poly(I:C)] is a synthetic mimetic of dsRNA and functions through an endosomal receptor, Toll-like receptor (TLR) 3 or cytosolic receptors. Another type of dsRNA, polyadeny...

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Bibliographic Details
Published in:International immunology 2008-01, Vol.20 (1), p.1-9
Main Authors: Sugiyama, Takahiro, Hoshino, Katsuaki, Saito, Masuyoshi, Yano, Takahiro, Sasaki, Izumi, Yamazaki, Chihiro, Akira, Shizuo, Kaisho, Tsuneyasu
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - pharmacology
Animals
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - metabolism
dendritic cell
Dendritic Cells - immunology
Dendritic Cells - metabolism
double-stranded RNA
immune adjuvant
Interferon-alpha - metabolism
Interferon-gamma - metabolism
Interleukin-12 Subunit p40 - metabolism
Membrane Glycoproteins - metabolism
Mice
Mice, Inbred C57BL
Poly A-U - pharmacology
RNA, Double-Stranded - pharmacology
Toll-like receptor
Toll-Like Receptor 3 - metabolism
Toll-Like Receptor 7 - metabolism
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Summary:Double-stranded RNA (dsRNA) is produced upon viral infection and can activate innate immunity. Polyinosinic:polycytidylic acids [poly(I:C)] is a synthetic mimetic of dsRNA and functions through an endosomal receptor, Toll-like receptor (TLR) 3 or cytosolic receptors. Another type of dsRNA, polyadenylic:polyuridylic acids [poly(A:U)], can also act as an immune adjuvant, but it remains unclear how it exhibits its adjuvant effects. Here, we have characterized the adjuvant effects of poly(A:U). Poly(A:U) could induce both IFN-α and IL-12p40 from murine bone marrow dendritic cells (DCs). Poly(A:U)-induced IFN-α production depended on a DC subset, plasmacytoid dendritic cell (pDC), and required TLR7. IL-12p40 was also produced by poly(A:U)-stimulated pDC in a TLR7-dependent manner. In addition to pDC, conventional dendritic cell (cDC) also produced IL-12p40 in response to poly(A:U). This IL-12p40 induction resulted from two cDC subsets, CD24high cDC and CD11bhigh cDC in a TLR3- and TLR7-dependent manner, respectively. In vivo injection of poly(A:U) with antigen led to clonal expansion of and IFN-γ production from antigen-specific CD8+ T cells. Consistent with the in vitro findings, TLR3 and TLR7 were required for the clonal T-cell expansion. Notably, TLR3, rather than TLR7, was critical for generating IFN-γ-producing CD8+ T cells. CD8+ T-cell responses induced by poly(A:U) were independent of type I IFN signaling. Our results demonstrate that poly(A:U) functions as an in vivo immunoadjuvant mainly through TLR3 and TLR7.
ISSN:0953-8178
1460-2377
DOI:10.1093/intimm/dxm112