Evidence for a DC-Specific Inhibitory Mechanism that Depends on MyD88 and SIGIRR

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...

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Bibliographic Details
Published in:Scandinavian journal of immunology 2010-06, Vol.71 (6), p.393-402
Main Authors: Drexler, S.K, Wales, J, Andreakos, E, Kong, P, Davis, A, Garlanda, C, Mantovani, A, Hussell, T, Feldmann, M, Foxwell, B.M.J
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - pharmacology
Animals
Antibodies, Viral - blood
Dendritic Cells - drug effects
Dendritic Cells - immunology
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 - immunology
Myeloid Differentiation Factor 88 - pharmacology
Receptors, Interleukin-1 - immunology
Specific Pathogen-Free Organisms
Th1 Cells - immunology
Vaccination - methods
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Summary: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.
ISSN:0300-9475
1365-3083
DOI:10.1111/j.1365-3083.2010.02392.x