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Scand J Immunol ; 71(6): 393-402, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20500691

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.


Subject(s)
Dendritic Cells/immunology , Myeloid Differentiation Factor 88/immunology , Receptors, Interleukin-1/immunology , Adjuvants, Immunologic/pharmacology , Animals , Antibodies, Viral/blood , Dendritic Cells/drug effects , Female , Humans , Immunity, Innate/immunology , Influenza A virus/immunology , Influenza Vaccines/immunology , Influenza Vaccines/pharmacology , Influenza, Human/immunology , Influenza, Human/prevention & control , Influenza, Human/virology , Mice , Mice, Inbred BALB C , Mice, Knockout , Myeloid Differentiation Factor 88/pharmacology , Specific Pathogen-Free Organisms , Th1 Cells/immunology , Vaccination/methods
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