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 degrees C (tetraacylated) versus ambient temperature (hexaacylated).


METHODS
Human monocytes and monocyte-derived dendritic cells (DCs) were exposed to Y. pestis grown at 26 degrees C or 37 degrees C, to their corresponding lipopolysaccharides (LPS-26 degrees C or LPS-37 degrees 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 degrees C or LPS-37 degrees C induced much lower production of cytokines (such as tumor necrosis factor alpha and interleukins 1beta, 10, and 12) by DCs than did Y. pestis grown at 26 degrees C or LPS-26 degrees C. Expression of the surface markers HLA-DR, CD86, and CD40 by DCs was also reduced in response to treatment with LPS-37 degrees C compared with LPS-26 degrees C. Pretreatment of DCs with LPS-37 degrees C inhibited subsequent stimulation with LPS-26 degrees C, control LPS from E. coli, lipoprotein, or poly-IC.


CONCLUSIONS
LPS-37 degrees C can inhibit stimulation of DCs not only via TLR4 signaling but also via TLR2 and TLR3. [corrected]
Telepnev
Maxim V
MV
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
Klimpel
Gary R
GR
Haithcoat
Judith
J
Knirel
Yuriy A
YA
Anisimov
Andrey P
AP
Motin
Vladimir L
VL
D000215:Acylation; D051940:B7-2 Antigen / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D004926:Escherichia coli / Q000737:chemistry; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D015398:Signal Transduction; D013696:Temperature; D051193:Toll-Like Receptors / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D015010:Yersinia pestis / Q000276:immunology* / Q000378:metabolism
D051940:B7-2 Antigen; D019013:CD40 Antigens; C497964:CD86 protein, human; D016207:Cytokines; D006684:HLA-DR Antigens; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D011070:Poly I-C