Tetraacylated lipopolysaccharide of yersinia pestis can inhibit multiple toll-like receptor-mediated signaling pathways in human dendritic cells

Background: Yersinia pestis, the causative agent of plague, showed a temperature-dependent change in lipid A composition, with a reduced degree of acylation when bacteria were grown at 37°C (tetraacylated) versus ambient temperature (hexaacylated). Methods: Human monocytes and monocyte-derived dendritic cells (DCs) were exposed to Y. pestis grown at 26°C or 37°C, to their corresponding lipopolysaccharides (LPS-26°C or LPS-37°C), and to ligands of different Toll-like receptors (TLRs), such as LPS from Escherichia coli (TLR4), lipoprotein (TLR2), polyinosinic-polycytidylic acid (poly-IC) (TLR9), and their combinations. Production of cytokines was measured, along with expression of surface markers of DC maturation. Results: Y. pestis grown at 37°C or LPS-37°C induced much lower production of cytokines (such as tumor necrosis factor α and interleukins 1β, 10, and 12) by DCs than did Y. pestis grown at 26°C or LPS-26°C. Expression of the surface markers HLA-DR, CD86, and CD40 by DCs was also reduced in response to treatment with LPS-37°C compared with LPS-26°C. Pretreatment of DCs with LPS-37°C inhibited subsequent stimulation with LPS-26°C, control LPS from E. coli, lipoprotein, or poly-IC. Conclusions: LPS-37°C can inhibit stimulation of DCs not only via TLR4 signaling but also via TLR2 and TLR9.