TY - JOUR
T1 - Evidence for a DC-specific inhibitory mechanism that depends on MyD88 and SIGIRR
AU - Drexler, S. K.
AU - Wales, J.
AU - Andreakos, E.
AU - Kong, P.
AU - Davis, A.
AU - Garlanda, C.
AU - Mantovani, A.
AU - Hussell, T.
AU - Feldmann, M.
AU - Foxwell, B. M J
PY - 2010/6
Y1 - 2010/6
N2 - 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.
AB - 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.
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U2 - 10.1111/j.1365-3083.2010.02392.x
DO - 10.1111/j.1365-3083.2010.02392.x
M3 - Article
C2 - 20500691
AN - SCOPUS:77952265563
VL - 71
SP - 393
EP - 402
JO - Scandinavian Journal of Immunology
JF - Scandinavian Journal of Immunology
SN - 0300-9475
IS - 6
ER -