Cutting edge: TLR2 directly triggers Th1 effector functions.
Toll-like receptors recognize pathogen-associated molecular patterns, activate innate immunity, and consequently modulate adaptive immunity in response to infections. TLRs are also expressed on T cells, and it has been shown that T cell activation is modulated by TLR ligands. However, the functions of TLRs on Th1 and Th2 effector cells and the molecular mechanisms underlying TLR-mediated activation are not fully understood. We analyzed TLR functions and downstream signaling events in both effector T cells. In mouse Th1 cells the stimulation by TLR2 but not by other TLRs directly induced IFN-gamma production, cell proliferation, and cell survival without TCR stimulation, and these effects were greatly enhanced by IL-2 or IL-12 through the enhanced activation of MAPKs. In contrast, no TLR affected the function of effector Th2 cells. These results identify TLR2 as a new specific activator of Th1 cell function and imply the involvement in Th1-mediated responses.
Imanishi
Takayuki
T
Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan.
Hara
Hiromitsu
H
Suzuki
Shinobu
S
Suzuki
Nobutaka
N
Akira
Shizuo
S
Saito
Takashi
T
D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival / Q000276:immunology; D004789:Enzyme Activation / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000502:physiology; D007376:Interleukin-2 / Q000502:physiology; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation / Q000276:immunology
D007376:Interleukin-2; D008024:Ligands; D051195:Toll-Like Receptor 2; D018664:Interleukin-12; D007371:Interferon-gamma; D048049:Extracellular Signal-Regulated MAP Kinases