High susceptibility of human dendritic cells to avian influenza H5N1 virus infection and protection by IFN-alpha and TLR ligands.
There is worldwide concern that the avian influenza H5N1 virus, with a mortality rate of >50%, might cause the next influenza pandemic. Unlike most other influenza infections, H5N1 infection causes a systemic disease. The underlying mechanisms for this effect are still unclear. In this study, we investigate the interplay between avian influenza H5N1 and human dendritic cells (DC). We showed that H5N1 virus can infect and replicate in monocyte-derived and blood myeloid DC, leading to cell death. These results suggest that H5N1 escapes viral-specific immunity, and could disseminate via DC. In contrast, blood pDC were resistant to infection and produced high amounts of IFN-alpha. Addition of this cytokine to monocyte-derived DC or pretreatment with TLR ligands protected against infection and the cytopathic effects of H5N1 virus.
Thitithanyanont
Arunee
A
Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
Engering
Anneke
A
Ekchariyawat
Peeraya
P
Wiboon-ut
Suwimon
S
Limsalakpetch
Amporn
A
Yongvanitchit
Kosol
K
Kum-Arb
Utaiwan
U
Kanchongkittiphon
Watcharoot
W
Utaisincharoen
Pongsak
P
Sirisinha
Stitaya
S
Puthavathana
Pilaipan
P
Fukuda
Mark M
MM
Pichyangkul
Sathit
S
D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism; D001717:Birds; D019070:Cell Lineage / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003588:Cytopathogenic Effect, Viral / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D004198:Disease Susceptibility / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology* / Q000472:pathogenicity; D005585:Influenza in Birds / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D016898:Interferon-alpha / Q000378:metabolism* / Q000502:physiology; D008024:Ligands; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D051196:Toll-Like Receptor 3 / Q000378:metabolism / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000378:metabolism / Q000502:physiology; D051193:Toll-Like Receptors / Q000378:metabolism* / Q000502:physiology; D014779:Virus Replication / Q000276:immunology
D000998:Antiviral Agents; D016898:Interferon-alpha; D008024:Ligands; D008070:Lipopolysaccharides; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors