Toll-like receptors 1 and 2 cooperatively mediate immune responses to curli, a common amyloid from enterobacterial biofilms.
Responses to host amyloids and curli amyloid fibrils of Escherichia coli and Salmonella enterica serotype Typhimurium are mediated through Toll-like receptor (TLR) 2. Here we show that TLR2 alone was not sufficient for mediating responses to curli. Instead, transfection experiments with human cervical cancer (HeLa) cells and antibody-mediated inhibition of TLR signalling in human macrophage-like (THP-1) cells suggested that TLR2 interacts with TLR1 to recognize curli amyloid fibrils. TLR1/TLR2 also serves as a receptor for tri-acylated lipoproteins, which are produced by E. coli and other Gram-negative bacteria. Despite the presence of multiple TLR1/TLR2 ligands on intact bacterial cells, an inability to produce curli amyloid fibrils markedly reduced the ability of E. coli to induce TLR2-dependent responses in vitro and in vivo. Collectively, our data suggest that curli amyloid fibrils from enterobacterial biofilms significantly contribute to TLR1/TLR2-mediated host responses against intact bacterial cells.
Tükel
Cagla
C
Temple University, School of Medicine, Department of Microbiology and Immunology, 3400N. Broad St. Kresge 502, Philadelphia, PA 19140, USA.
Nishimori
Jessalyn H
JH
Wilson
R Paul
RP
Winter
Maria G
MG
Keestra
A Marijke
AM
van Putten
Jos P M
JP
Bäumler
Andreas J
AJ
D000682:Amyloid / Q000276:immunology* / Q000378:metabolism; D001426:Bacterial Proteins / Q000276:immunology* / Q000378:metabolism; D018441:Biofilms; D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D004926:Escherichia coli / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D012486:Salmonella typhimurium / Q000276:immunology* / Q000378:metabolism; D051194:Toll-Like Receptor 1 / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology*
D000682:Amyloid; D001426:Bacterial Proteins; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; C077481:Crl protein, Bacteria