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

Fingerprint

Lipopeptides
Mycoplasma
Natural Killer Cells
Dendritic Cells
Lipoproteins
Myeloid Cells
Macrophages
Interleukin-6
Interleukin-12 Subunit p40
Cytokines
Amino Acids
Toll-Like Receptor 2
Palmitic Acid
Immunotherapy
Lipids
Peptides
Growth

Keywords

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

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Failure of mycoplasma lipoprotein MALP-2 to induce NK cell activation through dendritic cell TLR2. / Sawahata, Ryoko; Shime, Hiroaki; Yamazaki, Sayuri; Inoue, Norimitsu; Akazawa, Takashi; Fujimoto, Yukari; Fukase, Koichi; Matsumoto, Misako; Seya, Tsukasa.

In: Microbes and Infection, Vol. 13, No. 4, 04.2011, p. 350-358.

Research output: Contribution to journalArticle

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, vol. 13, no. 4, pp. 350-358. https://doi.org/10.1016/j.micinf.2010.12.003
Sawahata, Ryoko ; Shime, Hiroaki ; Yamazaki, Sayuri ; Inoue, Norimitsu ; Akazawa, Takashi ; Fujimoto, Yukari ; Fukase, Koichi ; Matsumoto, Misako ; Seya, Tsukasa. / Failure of mycoplasma lipoprotein MALP-2 to induce NK cell activation through dendritic cell TLR2. In: Microbes and Infection. 2011 ; Vol. 13, No. 4. pp. 350-358.
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