title: Plasmacytoid dendritic cells and Toll-like receptor 7-dependent signalling promote efficient protection of mice against highly virulent influenza A virus.
abstract: Types I and III interferons (IFNs) elicit protective antiviral immune responses during influenza virus infection. Although many cell types can synthesize IFN in response to virus infection, it remains unclear which IFN sources contribute to antiviral protection in vivo. We found that mice carrying functional alleles of the Mx1 influenza virus resistance gene partially lost resistance to infection with a highly pathogenic H7N7 influenza A virus strain if Toll-like receptor 7 (TLR7) signalling was compromised. This effect was achieved by deleting either the TLR7 gene or the gene encoding the TLR7 adaptor molecule MyD88. A similar decrease of influenza virus resistance was observed when animals were deprived of plasmacytoid dendritic cells (pDCs) at day 1 post-infection. Our results provide in vivo proof that pDCs contribute to the protection of the lung against influenza A virus infections, presumably via signals from TLR7.
authors.affiliation: Department of Virology, University of Freiburg, D-79104 Freiburg, Germany.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Kaminski
authors.affiliation: Department of Virology, University of Freiburg, D-79104 Freiburg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Ohnemus
authors.affiliation: Department of Virology, University of Freiburg, D-79104 Freiburg, Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Cornitescu
authors.affiliation: Department of Virology, University of Freiburg, D-79104 Freiburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Staeheli
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D060467:Disease Resistance / Q000276:immunology; D005260:Female; D017353:Gene Deletion; D053126:Influenza A Virus, H7N7 Subtype / Q000276:immunology* / Q000472:pathogenicity*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D015398:Signal Transduction; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000276:immunology*
chemical_list: D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7