Interferon-beta pretreatment of conventional and plasmacytoid human dendritic cells enhances their activation by influenza virus.
Influenza virus produces a protein, NS1, that inhibits infected cells from releasing type I interferon (IFN) and blocks maturation of conventional dendritic cells (DCs). As a result, influenza virus is a poor activator of both mouse and human DCs in vitro. However, in vivo a strong immune response to virus infection is generated in both species, suggesting that other factors may contribute to the maturation of DCs in vivo. It is likely that the environment in which a DC encounters a virus would contain multiple pro-inflammatory molecules, including type I IFN. Type I IFN is a critical component of the viral immune response that initiates an antiviral state in cells, primarily by triggering a broad transcriptional program that interferes with the ability of virus to establish infection in the cell. In this study, we have examined the activation profiles of both conventional and plasmacytoid dendritic cells (cDCs and pDCs) in response to an influenza virus infection in the context of a type I IFN-containing environment. We found that both cDCs and pDCs demonstrate a greater activation response to influenza virus when pre-exposed to IFN-beta (IFN priming); although, the priming kinetics are different in these two cell types. This strongly suggests that type I IFN functions not only to reduce viral replication in these immune cells, but also to promote greater DC activation during influenza virus infections.
Phipps-Yonas
Hannah
H
Department of Microbiology, Mount Sinai School of Medicine, New York, NY, USA.
Seto
Jeremy
J
Sealfon
Stuart C
SC
Moran
Thomas M
TM
Fernandez-Sesma
Ana
A
D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000502:physiology; D016899:Interferon-beta / Q000276:immunology*; D007700:Kinetics; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D051193:Toll-Like Receptors / Q000378:metabolism; D014158:Transcription, Genetic; D014758:Viral Core Proteins / Q000235:genetics; D017361:Viral Nonstructural Proteins / Q000378:metabolism; D014779:Virus Replication
C085820:INS1 protein, influenza virus; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins; D051193:Toll-Like Receptors; D014758:Viral Core Proteins; D017361:Viral Nonstructural Proteins; D016899:Interferon-beta