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

Ryoko Sawahata, Hiroaki Shime, Sayuri Yamazaki, Norimitsu Inoue, Takashi Akazawa, Yukari Fujimoto, Koichi Fukase, Misako Matsumoto, Tsukasa Seya

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)350-358
Number of pages9
JournalMicrobes and Infection
Volume13
Issue number4
DOIs
Publication statusPublished - 2011 Apr
Externally publishedYes

Keywords

  • Dendritic cells
  • Macrophage-activating lipopeptide 2
  • MyD88
  • NK activation
  • Toll-like receptor 2

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Infectious Diseases

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  • Cite this

    Sawahata, R., Shime, H., Yamazaki, S., Inoue, N., Akazawa, T., Fujimoto, Y., Fukase, K., Matsumoto, M., & Seya, T. (2011). Failure of mycoplasma lipoprotein MALP-2 to induce NK cell activation through dendritic cell TLR2. Microbes and Infection, 13(4), 350-358. https://doi.org/10.1016/j.micinf.2010.12.003