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

• Published in: Microbes and infection Vol. 13; no. 4; pp. 350 - 358
• Main Authors: Sawahata, Ryoko, Shime, Hiroaki, Yamazaki, Sayuri, Inoue, Norimitsu, Akazawa, Takashi, Fujimoto, Yukari, Fukase, Koichi, Matsumoto, Misako, Seya, Tsukasa
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier SAS 01.04.2011; Elsevier
• Subjects: Animals; Antineoplastic Agents - pharmacokinetics; Bacteriology; Biological and medical sciences; Cell Differentiation - drug effects; Cell Line, Tumor; Dendritic cells; Dendritic Cells - cytology; Dendritic Cells - drug effects; Female; Fundamental and applied biological sciences. Psychology; HEK293 Cells; Humans; Killer Cells, Natural - drug effects; Lipopeptides - pharmacology; Lymphocyte Activation - drug effects; Macrophage-activating lipopeptide 2; Melanoma, Experimental - physiopathology; Mice; Mice, Inbred C57BL; Mice, Knockout; Microbiology; Miscellaneous; Mycoplasma; Mycoplasma - chemistry; MyD88; Myeloid Differentiation Factor 88 - metabolism; NK activation; Toll-like receptor 2; Toll-Like Receptor 2 - immunology; Toll-Like Receptor 6 - immunology; Transplantation, Heterologous; NK activation; Macrophage-activating lipopeptide 2; Dendritic cells; Toll-like receptor 2; MyD88; Dendritic cell; Peptides; Toll like receptor 2; Lipoprotein; Mycoplasma; Mycoplasmataceae; Mollicutes; Natural killer cell; Mycoplasmatales; Bacteria; Failure; Lipopeptide; Macrophage
• ISSN: 1286-4579; 1769-714X
• DOI: 10.1016/j.micinf.2010.12.003

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.