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Failure of mycoplasma lipoprotein MALP-2 to induce NK cell activation through dendritic cell TLR2

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Title: Failure of mycoplasma lipoprotein MALP-2 to induce NK cell activation through dendritic cell TLR2
Authors: Sawahata, Ryoko Browse this author
Shime, Hiroaki Browse this author
Yamazaki, Sayuri Browse this author
Inoue, Norimitsu Browse this author
Akazawa, Takashi Browse this author
Fujimoto, Yukari Browse this author
Fukase, Koichi Browse this author
Matsumoto, Misako Browse this author
Seya, Tsukasa Browse this author
Keywords: Toll-like receptor 2
Macrophage-activating lipopeptide 2
Dendritic cells
NK activation
Issue Date: Apr-2011
Publisher: Elsevier Masson SAS
Journal Title: Microbes and Infection
Volume: 13
Issue: 4
Start Page: 350
End Page: 358
Publisher DOI: 10.1016/j.micinf.2010.12.003
PMID: 21172450
Abstract: 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.
Type: article (author version)
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 瀬谷 司

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