Activation of toll-like receptor 2 on human dendritic cells triggers induction of IL-12, but not IL-10.
Mammalian Toll-like receptors (TLRs) are required for cell activation by bacterial lipoproteins (bLP) and LPS. Stimulation of monocytes with bLP and LPS results in a TLR-dependent induction of immunomodulatory genes leading to the production of pro-inflammatory cytokines. In this paper, we compared the expression and response of TLRs on monocytes and dendritic cells (DC). TLR2, but not TLR4, was detected on peripheral blood monocytes and DC, in lymphoid tissue CD1alpha+ DC as well as on in vitro monocyte-derived DC. Upon stimulation with bLP or LPS, monocytes produced IL-12 and IL-10 at similar levels, whereas monocyte-derived DC produced comparable levels of IL-12, but little IL-10. Greater than 90% of the bLP-induced production of IL-12 was blocked by anti-TLR2 mAb. Thus, DC express TLR2 and activation of this receptor by bLP provides an innate mechanism by which microbial pathogens preferentially activate cell-mediated immunity.
Thoma-Uszynski
S
S
Division of Dermatology, University of California, Los Angeles, School of Medicine, 90095, USA.
Kiertscher
S M
SM
Ochoa
M T
MT
Bouis
D A
DA
Norgard
M V
MV
Miyake
K
K
Godowski
P J
PJ
Roth
M D
MD
Modlin
R L
RL
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000494:pharmacology; D001426:Bacterial Proteins / Q000138:chemical synthesis / Q000494:pharmacology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D029721:Drosophila Proteins; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000502:physiology; D008074:Lipoproteins / Q000138:chemical synthesis / Q000494:pharmacology; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism* / Q000502:physiology; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism* / Q000502:physiology; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001426:Bacterial Proteins; D029721:Drosophila Proteins; D015850:Interleukin-6; D008074:Lipoproteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12