title: Evidence for a DC-specific inhibitory mechanism that depends on MyD88 and SIGIRR.
abstract: Dendritic cells (DC) are an essential link between the innate and adaptive immune response. To become effective antigen-presenting cells DC need to undergo maturation, during which they up-regulate co-stimulatory molecules and produce cytokines. There is great interest in utilizing DC in vaccination regimes. Over recent years, Toll-like receptor (TLR) signalling has been recognized to be one of the major inducers of DC maturation. This study describes a mutant version of the TLR adaptor molecule MyD88 (termed MyD88lpr) as a novel adjuvant for vaccination regimes. MyD88lpr specifically activates DC by disrupting a DC intrinsic inhibitory mechanism, which is dependent on single immunoglobulin IL-1R-related. Moreover, MyD88lpr was able to induce an IgG2a-dominated response to a co-expressed antigen, suggesting Th1 immunity. However, when used as a vaccine adjuvant for Influenza nucleoprotein there was no significant difference in the lung viral titres during the infection. This study describes MyD88lpr as a potential adjuvant for vaccinations, which would be able to target DC specifically.
authors.affiliation: Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College London, Hammersmith, London, UK.
authors.forename: S K
authors.initials: SK
authors.lastname: Drexler
authors.forename: J
authors.initials: J
authors.lastname: Wales
authors.forename: E
authors.initials: E
authors.lastname: Andreakos
authors.forename: P
authors.initials: P
authors.lastname: Kong
authors.forename: A
authors.initials: A
authors.lastname: Davis
authors.forename: C
authors.initials: C
authors.lastname: Garlanda
authors.forename: A
authors.initials: A
authors.lastname: Mantovani
authors.forename: T
authors.initials: T
authors.lastname: Hussell
authors.forename: M
authors.initials: M
authors.lastname: Feldmann
authors.forename: B M J
authors.initials: BM
authors.lastname: Foxwell
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology / Q000494:pharmacology; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology* / Q000494:pharmacology; D017472:Receptors, Interleukin-1 / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D018417:Th1 Cells / Q000276:immunology; D014611:Vaccination / Q000379:methods
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D053594:Myeloid Differentiation Factor 88; D017472:Receptors, Interleukin-1; C484529:SIGIRR protein, mouse