TY - JOUR
T1 - Failure of mycoplasma lipoprotein MALP-2 to induce NK cell activation through dendritic cell TLR2
AU - Sawahata, Ryoko
AU - Shime, Hiroaki
AU - Yamazaki, Sayuri
AU - Inoue, Norimitsu
AU - Akazawa, Takashi
AU - Fujimoto, Yukari
AU - Fukase, Koichi
AU - Matsumoto, Misako
AU - Seya, Tsukasa
N1 - Funding Information:
We thank Drs. J. Kasamatsu, H. Takaki, A. H. Hussein, A. Watanabe and H. Oshiumi in our laboratory for their critical discussions. This work was supported in part by Grants-in-Aid from the Ministry of Education, Science, and Culture (Specified Project for Advanced Research) and the Ministry of Health, Labor, and Welfare of Japan , and by the Yakult and Waxmann Foundations . Financial supports by the Sapporo Biocluster “Bio-S” the Knowledge Cluster Initiative of the MEXT , is gratefully acknowledged.
PY - 2011/4
Y1 - 2011/4
N2 - Macrophage-activating lipopeptide 2 (MALP-2), a mycoplasmal diacylated lipopeptide with palmitic acid moiety (Pam2), activates Toll-like receptor (TLR) 2 to induce inflammatory cytokines. TLR2 is known to mature myeloid dendritic cells (mDC) to drive mDC contact-mediated natural killer (NK) cell activation. Here we tested if MALP-2 activates NK cells through stimulation of TLR2 on mDC. Although synthetic MALP-2 with 6 or 14 amino acids (a.a.) stretch (designated as s and f) matured mDC to induce IL-6, IL-12p40 and TNF-α to a similar extent, they far less activated NK cells than Pam2CSK4, a positive control of 6 a.a.-containing diacyl lipopeptide. MALP-2s and f were TLR2/6 agonists and activate the MyD88 pathway similar to Pam2CSK4, but MALP-2s having the CGNNDE sequence acted on mDC TLR2 to barely induce external NK activation. Even the s form, with slightly high induction of IL-6 compared to the f form, barely induced in vivo growth retardation of NK-sensitive implant tumor. Pam2CSK4 and MALP-2 have the common lipid moiety but different peptides, which are crucial for NK cell activation. The results infer that MALP-2 is applicable to a cytokine inducer but not to an adjuvant for antitumor NK immunotherapy.
AB - Macrophage-activating lipopeptide 2 (MALP-2), a mycoplasmal diacylated lipopeptide with palmitic acid moiety (Pam2), activates Toll-like receptor (TLR) 2 to induce inflammatory cytokines. TLR2 is known to mature myeloid dendritic cells (mDC) to drive mDC contact-mediated natural killer (NK) cell activation. Here we tested if MALP-2 activates NK cells through stimulation of TLR2 on mDC. Although synthetic MALP-2 with 6 or 14 amino acids (a.a.) stretch (designated as s and f) matured mDC to induce IL-6, IL-12p40 and TNF-α to a similar extent, they far less activated NK cells than Pam2CSK4, a positive control of 6 a.a.-containing diacyl lipopeptide. MALP-2s and f were TLR2/6 agonists and activate the MyD88 pathway similar to Pam2CSK4, but MALP-2s having the CGNNDE sequence acted on mDC TLR2 to barely induce external NK activation. Even the s form, with slightly high induction of IL-6 compared to the f form, barely induced in vivo growth retardation of NK-sensitive implant tumor. Pam2CSK4 and MALP-2 have the common lipid moiety but different peptides, which are crucial for NK cell activation. The results infer that MALP-2 is applicable to a cytokine inducer but not to an adjuvant for antitumor NK immunotherapy.
KW - Dendritic cells
KW - Macrophage-activating lipopeptide 2
KW - MyD88
KW - NK activation
KW - Toll-like receptor 2
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U2 - 10.1016/j.micinf.2010.12.003
DO - 10.1016/j.micinf.2010.12.003
M3 - Article
C2 - 21172450
AN - SCOPUS:79952451366
SN - 1286-4579
VL - 13
SP - 350
EP - 358
JO - Microbes and Infection
JF - Microbes and Infection
IS - 4
ER -
