Autophagy-Dependent Viral Recognition by Plasmacytoid Dendritic Cells

@article{Lee2007AutophagyDependentVR,
  title={Autophagy-Dependent Viral Recognition by Plasmacytoid Dendritic Cells},
  author={Heung Kyu Lee and Jennifer M. Lund and Balaji Ramanathan and Noboru Mizushima and Akiko Iwasaki},
  journal={Science},
  year={2007},
  volume={315},
  pages={1398 - 1401}
}
Plasmacytoid dendritic cells (pDCs) detect viruses in the acidified endosomes by means of Toll-like receptors (TLRs). Yet, pDC responses to certain single-stranded RNA (ssRNA) viruses occur only after live viral infection. We present evidence here that the recognition of such viruses by TLR7 requires transport of cytosolic viral replication intermediates into the lysosome by the process of autophagy. In addition, autophagy was found to be required for the production of interferon-α by pDCs… 
Role of Autophagy in Innate Viral Recognition
TLDR
Results indicated that autophagy plays a key role in mediating virus detection and IFNα secretion in pDCs, and suggest that cytosolic replication intermediates of ssRNA viruses serve as pathogen signatures recognized by TLR7.
Autophagy and innate immunity to viruses
TLDR
Findings indicate that autophagy may deliver viral replication intermediates located in the cytosol to Toll-like receptors located inThe endosome to trigger cytokine production.
Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases
TLDR
Several pDC receptors negatively regulate type I IFN responses by pDCs during viral infection and for normal homeostasis, which normally prevents pDC responses to them.
Regulation of TLR7/9 signaling in plasmacytoid dendritic cells
TLDR
This review focuses on TLR7/9 signaling and their regulation by pDC-specific receptors, which have been implicated not only in antiviral innate immunity but also in immune tolerance, inflammation and tumor microenvironments.
Beclin-1 Targeting for Viral Immune Escape
TLDR
Inhibition of macroautophagy either before or after autophagosome formation seems to benefit their viral replication by different mechanisms, which are discussed here.
Virus interactions with endocytic pathways in macrophages and dendritic cells.
TLDR
Mechanisms by which viruses subvert endocytic and pathogen-sensing functions of macrophages and DCs are reviewed, while highlighting possible strategic advantages of infecting cells normally tuned into pathogen destruction.
Viral evasion of autophagy
TLDR
The current understanding of autophagy as an antiviral pathway is summarized, and strategies that viruses may utilize to evade this host defense mechanism are discussed.
The multifaceted biology of plasmacytoid dendritic cells
TLDR
Recent progress in the field of pDC biology is summarized, focusing on the molecular mechanisms that regulate the development and functions of p DCs, the pathways involved in their sensing of pathogens and endogenous nucleic acids, their functions at mucosal sites, and their roles in infection, autoimmunity and cancer.
Autophagy and antiviral immunity
TLDR
Recent advances in the field of autophagy are described as it relates to innate and adaptive antiviral immune responses, allowing activation of CD4 T cells.
Short-range exosomal transfer of viral RNA from infected cells to plasmacytoid dendritic cells triggers innate immunity.
Viral nucleic acids often trigger an innate immune response in infected cells. Many viruses, including hepatitis C virus (HCV), have evolved mechanisms to evade intracellular recognition.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 29 REFERENCES
Innate Antiviral Responses by Means of TLR7-Mediated Recognition of Single-Stranded RNA
TLDR
These results identify ssRNA as a ligand for TLR7 and suggest that cells of the innate immune system sense endosomal ssRNA to detect infection by RNA viruses.
Endocytosis of HIV-1 activates plasmacytoid dendritic cells via Toll-like receptor-viral RNA interactions.
TLDR
It is demonstrated by in vitro studies that IFN-alpha production by pDC in response to HIV-1 requires at least 2 interactions between the cell and virus, and that TLR7 is the likely primary target.
Replication-Dependent Potent IFN-α Induction in Human Plasmacytoid Dendritic Cells by a Single-Stranded RNA Virus1
TLDR
It is confirmed that a ssRNA virus, which is able to directly enter host cells via fusion at the plasma membrane, can be detected by PDC independently of PKR, TLR7/8, and TLR9.
Subversion of Cellular Autophagosomal Machinery by RNA Viruses
TLDR
It is argued that these double-membraned structures provide membranous supports for viral RNA replication complexes, possibly enabling the nonlytic release of cytoplasmic contents, including progeny virions, from infected cells.
Toll-like Receptor 9–mediated Recognition of Herpes Simplex Virus-2 by Plasmacytoid Dendritic Cells
TLDR
A novel mechanism whereby the genomic DNA of a virus can engage TLR9 and result in the secretion of IFN-α by pDCs is demonstrated.
Cell type-specific involvement of RIG-I in antiviral response.
TLDR
It is shown by gene targeting that RIG-I is essential for induction of type I interferons (IFNs) after infection with RNA viruses in fibroblasts and conventional dendritic cells (DCs) and exert antiviral responses in a cell type-specific manner.
Recognition of single-stranded RNA viruses by Toll-like receptor 7.
TLDR
It is shown that TLR7 recognizes the single-stranded RNA viruses, vesicular stomatitis virus and influenza virus, and insights into the pathways used by the innate immune cells in the recognition of viral pathogens are provided.
Species-Specific Recognition of Single-Stranded RNA via Toll-like Receptor 7 and 8
TLDR
It is shown that guanosine (G)- and uridine (U)-rich ssRNA oligonucleotides derived from human immunodeficiency virus–1 (HIV-1) stimulate dendritic cells and macrophages to secrete interferon-α and proinflammatory, as well as regulatory, cytokines, and these data suggest that ssRNA represents a physiological ligand for TLR7 and TLR8.
TLR7: A new sensor of viral infection.
  • K. Crozat, B. Beutler
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 2004
TLDR
Lund et al. (5) provide a more complete picture of what the TLRs do and are left with several important questions, as discussed below.
Autophagosome formation in mammalian cells.
TLDR
Identification and characterization of the mammalian counterparts of the yeast autophagy proteins has facilitated understanding of mammalian autophapy, particularly of autophagosome formation, and these findings are now being applied to studies on the physiological roles of Autophagy in mammals.
...
1
2
3
...