The diacylated lipopeptide FSL-1 enhances phagocytosis of bacteria by macrophages through a Toll-like receptor 2-mediated signalling pathway.
A significant amount of evidence has been accumulated to show that Toll-like receptors (TLRs) function as sensors for microbial invasion. However, little is known about how signalling triggered by TLRs leads to the phagocytosis of pathogens. This study was designed to determine whether stimulation of TLR2 mainly with the lipopeptide FSL-1 plays a role in the phagocytosis of pathogens by macrophages. FSL-1 enhanced the phagocytosis of Escherichia coli to a markedly greater extent than it did that of Staphylococcus aureus, but did not enhance the phagocytosis of latex beads. FSL-1 stimulation resulted in enhanced phagocytosis of bacteria by macrophages from TLR2(+/+) mice but not by those from TLR2(-/-) mice. Chinese hamster ovary cells stably expressing TLR2 failed to phagocytose these bacteria, but the cells expressing CD14 did. FSL-1 induced upregulation of the expression of phagocytic receptors, including MSR1, CD36, DC-SIGN and Dectin-1 in THP-1 cells. Human embryonic kidney 293 cells transfected with DC-SIGN and MSR1 phagocytosed these bacteria. These results suggest that the FSL-1-induced enhancement of phagocytosis of bacteria by macrophages may be explained partly by the upregulation of scavenger receptors and the C-type lectins through TLR2-mediated signalling pathways, and that TLR2 by itself does not function as a phagocytic receptor.
Mae
Masako
M
Laboratory of Oral Molecular Microbiology, Department of Oral Pathobiological Science, Hokkaido University Graduate School of Dental Medicine, Kita, Sapporo, Japan.
Iyori
Mitsuhiro
M
Yasuda
Motoaki
M
Shamsul
Haque Mohammad
HM
Kataoka
Hideo
H
Kiura
Kazuto
K
Hasebe
Akira
A
Totsuka
Yasunori
Y
Shibata
Ken-Ichiro
K
D000818:Animals; D001419:Bacteria / Q000276:immunology*; D016466:CHO Cells; D002460:Cell Line; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004075:Diglycerides / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology; D005260:Female; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008863:Microspheres; D009842:Oligopeptides / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology*; D011971:Receptors, Immunologic / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013211:Staphylococcus aureus / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology*
D004075:Diglycerides; C460864:FSL-1 lipoprotein, synthetic; D018950:Lipopolysaccharide Receptors; D009842:Oligopeptides; D011971:Receptors, Immunologic; D051195:Toll-Like Receptor 2; C028495:phagocytosis receptor