MyD88-Dependent SHIP1 Regulates Proinflammatory Signaling Pathways in Dendritic Cells after Monophosphoryl Lipid A Stimulation of TLR4

摘要: We previously showed that monophosphoryl lipid A (MLA) activates TLR4 in dendritic cells (DCs) a Toll/IL-1R domain-containing adaptor inducing IFN-β (TRIF)–biased manner: MLA produced from Salmonella minnesota Re595 induced signaling events and expression of gene products were primarily TRIF dependent, whereas MyD88-dependent was impaired. Moreover, when tested TRIF-intact/MyD88-deficient DCs, synthetic the Escherichia coli chemotype (sMLA) same activity as its diphosphoryl, inflammatory counterpart (synthetic diphosphoryl A), indicating TRIF-mediated is fully by sMLA. Unexpectedly, we found transcript level one proinflammatory cytokine increased sMLA-treated MyD88 deficiency to higher A, which suggested may paradoxically help restrain TRIF-biased In this article, demonstrate sMLA induces recruitment anti-inflammatory phosphatase SHIP1 an manner. At time, at IL-1R–associated kinase 1 markedly reduced. Increased associated with reductions sMLA-induced IκB α/β IFN regulatory factor 3 activation restrained their downstream targets, endothelin-1 IFN-β, respectively. Results study identify pattern desirable context vaccine adjuvant design: can stimulate partial activity, helping reduce DCs.