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Autophagy-dependent viral recognition by plasmacytoid dendritic cells
Heung Kyu Lee1, Jennifer M Lund, Balaji Ramanathan
1Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
Science (New York, N.Y.)
|February 3, 2007
Summary
Autophagy transports viral RNA to lysosomes for detection by Toll-like receptor 7 (TLR7) in plasmacytoid dendritic cells (pDCs). This process is essential for interferon-alpha production, crucial for antiviral defense.
Area of Science:
- Immunology
- Cell Biology
- Virology
Background:
- Plasmacytoid dendritic cells (pDCs) use Toll-like receptors (TLRs) to detect viruses within acidified endosomes.
- pDC antiviral responses to some single-stranded RNA (ssRNA) viruses necessitate live viral infection.
Purpose of the Study:
- To investigate the mechanism by which pDCs recognize ssRNA viruses requiring live infection.
- To elucidate the role of autophagy in ssRNA virus recognition and interferon-alpha production by pDCs.
Main Methods:
- Investigated the role of autophagy in transporting cytosolic viral replication intermediates.
- Assessed the requirement of autophagy for TLR7-mediated recognition of ssRNA viruses.
- Measured interferon-alpha production by pDCs in response to viral infection.
Main Results:
- Autophagy is required to transport cytosolic viral replication intermediates into the lysosome for TLR7 recognition.
- Autophagy is essential for the production of interferon-alpha by pDCs.
- Viral replication intermediates act as pathogen signatures for TLR7 detection.
Conclusions:
- Autophagy plays a critical role in mediating the detection of ssRNA viruses by pDCs via TLR7.
- Autophagy is indispensable for interferon-alpha secretion, a key component of the innate immune response to viral infections.
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