Failure of mycoplasma lipoprotein MALP-2 to induce NK cell activation through dendritic cell TLR2
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 act...
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creator | Sawahata, Ryoko Shime, Hiroaki Yamazaki, Sayuri Inoue, Norimitsu Akazawa, Takashi Fujimoto, Yukari Fukase, Koichi Matsumoto, Misako Seya, Tsukasa |
description | 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. |
doi_str_mv | 10.1016/j.micinf.2010.12.003 |
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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.</description><identifier>ISSN: 1286-4579</identifier><identifier>EISSN: 1769-714X</identifier><identifier>DOI: 10.1016/j.micinf.2010.12.003</identifier><identifier>PMID: 21172450</identifier><language>eng</language><publisher>Kidlington: Elsevier SAS</publisher><subject>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</subject><ispartof>Microbes and infection, 2011-04, Vol.13 (4), p.350-358</ispartof><rights>2010 Institut Pasteur</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2010 Institut Pasteur. Published by Elsevier SAS. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c579t-debcc8452c35b11760c80553ca63eea1b7ab7b3641c652b3f13976d94886bb303</citedby><cites>FETCH-LOGICAL-c579t-debcc8452c35b11760c80553ca63eea1b7ab7b3641c652b3f13976d94886bb303</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.micinf.2010.12.003$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,778,782,3539,27907,27908,45978</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23968315$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21172450$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sawahata, Ryoko</creatorcontrib><creatorcontrib>Shime, Hiroaki</creatorcontrib><creatorcontrib>Yamazaki, Sayuri</creatorcontrib><creatorcontrib>Inoue, Norimitsu</creatorcontrib><creatorcontrib>Akazawa, Takashi</creatorcontrib><creatorcontrib>Fujimoto, Yukari</creatorcontrib><creatorcontrib>Fukase, Koichi</creatorcontrib><creatorcontrib>Matsumoto, Misako</creatorcontrib><creatorcontrib>Seya, Tsukasa</creatorcontrib><title>Failure of mycoplasma lipoprotein MALP-2 to induce NK cell activation through dendritic cell TLR2</title><title>Microbes and infection</title><addtitle>Microbes Infect</addtitle><description>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.</description><subject>Animals</subject><subject>Antineoplastic Agents - pharmacokinetics</subject><subject>Bacteriology</subject><subject>Biological and medical sciences</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Line, Tumor</subject><subject>Dendritic cells</subject><subject>Dendritic Cells - cytology</subject><subject>Dendritic Cells - drug effects</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Killer Cells, Natural - drug effects</subject><subject>Lipopeptides - pharmacology</subject><subject>Lymphocyte Activation - drug effects</subject><subject>Macrophage-activating lipopeptide 2</subject><subject>Melanoma, Experimental - physiopathology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Microbiology</subject><subject>Miscellaneous</subject><subject>Mycoplasma</subject><subject>Mycoplasma - chemistry</subject><subject>MyD88</subject><subject>Myeloid Differentiation Factor 88 - metabolism</subject><subject>NK activation</subject><subject>Toll-like receptor 2</subject><subject>Toll-Like Receptor 2 - immunology</subject><subject>Toll-Like Receptor 6 - immunology</subject><subject>Transplantation, Heterologous</subject><issn>1286-4579</issn><issn>1769-714X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUuLFDEURoMozkP_gUg24qravJPaCMPgOGL7QEZwF1K3Uk6aqkpPkhqYf2-aanWnq1zC-ZLD_RB6QcmGEqre7DZTgDAPG0YOV2xDCH-ETqlWbaOp-PG4zsyoRkjdnqCznHeEUKmVeIpOGKWaCUlOkbtyYVySx3HA0wPE_ejy5PAY9nGfYvFhxp8utl8bhkvEYe4X8PjzRwx-HLGDEu5dCXHG5TbF5ect7v3cp1ACrMTN9ht7hp4Mbsz--fE8R9-v3t1cXjfbL-8_XF5sG6iCpel9B2CEZMBlV_UUAUOk5OAU997RTrtOd1wJCkqyjg-Ut1r1rTBGdR0n_By9Xt-t3neLz8VOIR8s3Ozjkq0xhtQEF_8npaaMGaoqKVYSUsw5-cHuU5hcerCU2EMLdmfXFuyhBUuZrS3U2MvjB0s3-f5P6PfaK_DqCLgMbhySmyHkvxxvleFUVu7tyvm6uPvgk80Q_Ay-D8lDsX0M_zb5BfN0pgw</recordid><startdate>20110401</startdate><enddate>20110401</enddate><creator>Sawahata, Ryoko</creator><creator>Shime, Hiroaki</creator><creator>Yamazaki, Sayuri</creator><creator>Inoue, Norimitsu</creator><creator>Akazawa, Takashi</creator><creator>Fujimoto, Yukari</creator><creator>Fukase, Koichi</creator><creator>Matsumoto, Misako</creator><creator>Seya, Tsukasa</creator><general>Elsevier SAS</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QL</scope><scope>7T5</scope><scope>C1K</scope><scope>H94</scope></search><sort><creationdate>20110401</creationdate><title>Failure of mycoplasma lipoprotein MALP-2 to induce NK cell activation through dendritic cell TLR2</title><author>Sawahata, Ryoko ; Shime, Hiroaki ; Yamazaki, Sayuri ; Inoue, Norimitsu ; Akazawa, Takashi ; Fujimoto, Yukari ; Fukase, Koichi ; Matsumoto, Misako ; Seya, Tsukasa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c579t-debcc8452c35b11760c80553ca63eea1b7ab7b3641c652b3f13976d94886bb303</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - pharmacokinetics</topic><topic>Bacteriology</topic><topic>Biological and medical sciences</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Line, Tumor</topic><topic>Dendritic cells</topic><topic>Dendritic Cells - cytology</topic><topic>Dendritic Cells - drug effects</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Killer Cells, Natural - drug effects</topic><topic>Lipopeptides - pharmacology</topic><topic>Lymphocyte Activation - drug effects</topic><topic>Macrophage-activating lipopeptide 2</topic><topic>Melanoma, Experimental - physiopathology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Microbiology</topic><topic>Miscellaneous</topic><topic>Mycoplasma</topic><topic>Mycoplasma - chemistry</topic><topic>MyD88</topic><topic>Myeloid Differentiation Factor 88 - metabolism</topic><topic>NK activation</topic><topic>Toll-like receptor 2</topic><topic>Toll-Like Receptor 2 - immunology</topic><topic>Toll-Like Receptor 6 - immunology</topic><topic>Transplantation, Heterologous</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sawahata, Ryoko</creatorcontrib><creatorcontrib>Shime, Hiroaki</creatorcontrib><creatorcontrib>Yamazaki, Sayuri</creatorcontrib><creatorcontrib>Inoue, Norimitsu</creatorcontrib><creatorcontrib>Akazawa, Takashi</creatorcontrib><creatorcontrib>Fujimoto, Yukari</creatorcontrib><creatorcontrib>Fukase, Koichi</creatorcontrib><creatorcontrib>Matsumoto, Misako</creatorcontrib><creatorcontrib>Seya, Tsukasa</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Microbes and infection</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sawahata, Ryoko</au><au>Shime, Hiroaki</au><au>Yamazaki, Sayuri</au><au>Inoue, Norimitsu</au><au>Akazawa, Takashi</au><au>Fujimoto, Yukari</au><au>Fukase, Koichi</au><au>Matsumoto, Misako</au><au>Seya, Tsukasa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Failure of mycoplasma lipoprotein MALP-2 to induce NK cell activation through dendritic cell TLR2</atitle><jtitle>Microbes and infection</jtitle><addtitle>Microbes Infect</addtitle><date>2011-04-01</date><risdate>2011</risdate><volume>13</volume><issue>4</issue><spage>350</spage><epage>358</epage><pages>350-358</pages><issn>1286-4579</issn><eissn>1769-714X</eissn><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.</abstract><cop>Kidlington</cop><pub>Elsevier SAS</pub><pmid>21172450</pmid><doi>10.1016/j.micinf.2010.12.003</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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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 |
title | Failure of mycoplasma lipoprotein MALP-2 to induce NK cell activation through dendritic cell TLR2 |
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