A recombinant lipoprotein containing an unsaturated fatty acid activates NF-kappaB through the TLR2 signaling pathway and induces a differential gene profile from a synthetic lipopeptide.
The lipid moiety of a novel recombinant lipoprotein, which contains a dengue virus envelope protein domain 3, rlipo-D1E3, has been shown to activate antigen-presenting cells (APCs) as an intrinsic adjuvant. Because the lipid moiety of rlipo-D1E3 contains an unsaturated fatty acid, it is unclear if the receptor usage by bacterially derived lipoproteins is the same as that of the synthetic lipopeptide palmitoyl-3-Cys-Ser-(Lys)(4) (Pam3). In the present study, we show that the rlipo-D1E3 lipoprotein can induce the activation of spleen cells and bone marrow-derived dendritic cells (BM-DCs) in wild-type and TLR4-deficient mice, but not in TLR2(-/-) mice. After analyzing the co-receptor usage of TLR2 using TLR1(-/-) or TLR6(-/-) mice, the TLR2 signaling triggered by rlipo-D1E3 and Pam3 could use either TLR1 or TLR6 as a co-receptor. Analysis of the MAPK signaling pathway revealed that rlipo-D1E3 could initiate the phosphorylation of p38, ERK1/2 and JNK1/2 earlier than the synthetic lipopeptide. In addition, the expression levels of IL-23, IL-27 and MIP-1 alpha in BM-DCs stimulated by rlipo-D1E3 were higher than the expression levels in BM-DCs stimulated by Pam3. Taken together, these results demonstrate that different TLR2 ligands can promote various immune responses by inducing different levels of biological cytokines and chemokines.
Leng
Chih-Hsiang
CH
Vaccine Research and Development Center, National Health Research Institutes, Taiwan.
Chen
Hsin-Wei
HW
Chang
Li-Sheng
LS
Liu
Hsueh-Hung
HH
Liu
Hsin-Yu
HY
Sher
Yuh-Pyng
YP
Chang
Yu-Wen
YW
Lien
Shu-Pei
SP
Huang
Tzu-Yi
TY
Chen
Mei-Yu
MY
Chou
Ai-Hsiang
AH
Chong
Pele
P
Liu
Shih-Jen
SJ
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D018925:Chemokines / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D020869:Gene Expression Profiling; D008074:Lipoproteins / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D051195:Toll-Like Receptor 2 / Q000502:physiology*
D000276:Adjuvants, Immunologic; D018925:Chemokines; D016207:Cytokines; D008074:Lipoproteins; D016328:NF-kappa B; D011994:Recombinant Proteins; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2