Evidence for a DC-specific inhibitory mechanism that depends on MyD88 and SIGIRR

S. K. Drexler, J. Wales, E. Andreakos, P. Kong, A. Davis, C. Garlanda, A. Mantovani, T. Hussell, M. Feldmann, B. M J Foxwell

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)393-402
Number of pages10
JournalScandinavian Journal of Immunology
Volume71
Issue number6
DOIs
Publication statusPublished - Jun 2010

ASJC Scopus subject areas

  • Immunology

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