Penicillin binding proteins as danger signals: meningococcal penicillin binding protein 2 activates dendritic cells through Toll-like receptor 4
Neisseria meningitidis is a human pathogen responsible for life-threatening inflammatory diseases. Meningococcal penicillin-binding proteins (PBPs) and particularly PBP2 are involved in bacterial resistance to β-lactams. Here we describe a novel function for PBP2 that activates human and mouse dendr...
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| Veröffentlicht in: | PloS one 2011-10, Vol.6 (10), p.e23995 |
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| creator | Hill, Marcelo Deghmane, Ala-Eddine Segovia, Mercedes Zarantonelli, Maria Leticia Tilly, Gaëlle Blancou, Philippe Bériou, Gaëlle Josien, Régis Anegon, Ignacio Hong, Eva Ruckly, Corinne Antignac, Aude El Ghachi, Meriem Boneca, Ivo Gomperts Taha, Muhamed-Kheir Cuturi, Maria Cristina |
| description | Neisseria meningitidis is a human pathogen responsible for life-threatening inflammatory diseases. Meningococcal penicillin-binding proteins (PBPs) and particularly PBP2 are involved in bacterial resistance to β-lactams. Here we describe a novel function for PBP2 that activates human and mouse dendritic cells (DC) in a time and dose-dependent manner. PBP2 induces MHC II (LOGEC50 = 4.7 µg/ml ± 0.1), CD80 (LOGEC50 = 4.88 µg/ml ± 0.15) and CD86 (LOGEC50 = 5.36 µg/ml ± 0.1). This effect was abolished when DCs were co-treated with anti-PBP2 antibodies. PBP2-treated DCs displayed enhanced immunogenic properties in vitro and in vivo. Furthermore, proteins co-purified with PBP2 showed no effect on DC maturation. We show through different in vivo and in vitro approaches that this effect is not due to endotoxin contamination. At the mechanistic level, PBP2 induces nuclear localization of p65 NF-kB of 70.7 ± 5.1% cells versus 12 ± 2.6% in untreated DCs and needs TLR4 expression to mature DCs. Immunoprecipitation and blocking experiments showed thatPBP2 binds TLR4. In conclusion, we describe a novel function of meningococcal PBP2 as a pathogen associated molecular pattern (PAMP) at the host-pathogen interface that could be recognized by the immune system as a danger signal, promoting the development of immune responses. |
| doi_str_mv | 10.1371/journal.pone.0023995 |
| format | Article |
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Meningococcal penicillin-binding proteins (PBPs) and particularly PBP2 are involved in bacterial resistance to β-lactams. Here we describe a novel function for PBP2 that activates human and mouse dendritic cells (DC) in a time and dose-dependent manner. PBP2 induces MHC II (LOGEC50 = 4.7 µg/ml ± 0.1), CD80 (LOGEC50 = 4.88 µg/ml ± 0.15) and CD86 (LOGEC50 = 5.36 µg/ml ± 0.1). This effect was abolished when DCs were co-treated with anti-PBP2 antibodies. PBP2-treated DCs displayed enhanced immunogenic properties in vitro and in vivo. Furthermore, proteins co-purified with PBP2 showed no effect on DC maturation. We show through different in vivo and in vitro approaches that this effect is not due to endotoxin contamination. At the mechanistic level, PBP2 induces nuclear localization of p65 NF-kB of 70.7 ± 5.1% cells versus 12 ± 2.6% in untreated DCs and needs TLR4 expression to mature DCs. Immunoprecipitation and blocking experiments showed thatPBP2 binds TLR4. In conclusion, we describe a novel function of meningococcal PBP2 as a pathogen associated molecular pattern (PAMP) at the host-pathogen interface that could be recognized by the immune system as a danger signal, promoting the development of immune responses.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0023995</identifier><identifier>PMID: 22046231</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Antibiotics ; Antibodies ; B cells ; B7-1 Antigen ; B7-1 Antigen - biosynthesis ; B7-2 Antigen ; B7-2 Antigen - biosynthesis ; Bacteria ; Bacterial infections ; Bacteriology ; Binding ; Binding proteins ; Biology ; CD80 antigen ; CD86 antigen ; Cells, Cultured ; Contamination ; Dendritic Cells ; Dendritic Cells - immunology ; Dendritic Cells - microbiology ; Dose-Response Relationship, Drug ; Drug resistance ; Hazards ; Histocompatibility Antigens Class II ; Histocompatibility Antigens Class II - biosynthesis ; Host-Pathogen Interactions ; Host-Pathogen Interactions - immunology ; Human behavior ; Humans ; Immune response ; Immune system ; Immunogenicity ; Immunoprecipitation ; Inflammatory diseases ; Lactams ; Life Sciences ; Localization ; Major histocompatibility complex ; Maturation ; Medicine ; Mice ; Microbiology and Parasitology ; Neisseria meningitidis ; Neisseria meningitidis - chemistry ; Neisseria meningitidis - immunology ; NF-κB protein ; Pathogens ; Pattern recognition ; Penicillin ; Penicillin-Binding Proteins ; Penicillin-Binding Proteins - pharmacology ; Protein binding ; Proteins ; Rodents ; TLR4 protein ; Toll-Like Receptor 4 ; Toll-Like Receptor 4 - immunology ; Toll-like receptors ; Vaccines</subject><ispartof>PloS one, 2011-10, Vol.6 (10), p.e23995</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Hill et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Attribution</rights><rights>Hill et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c729t-142270ab6f495d4f757f2cb3a96736aab1b6e43ef048195c8aee46e45f0c05963</citedby><cites>FETCH-LOGICAL-c729t-142270ab6f495d4f757f2cb3a96736aab1b6e43ef048195c8aee46e45f0c05963</cites><orcidid>0000-0001-5249-7467 ; 0000-0002-9293-9685 ; 0000-0002-0716-3174 ; 0000-0003-0305-8622 ; 0000-0001-8700-5645 ; 0000-0003-2887-1732 ; 0000-0001-8122-509X ; 0000-0001-7900-7413 ; 0000-0002-1589-0320</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3203111/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3203111/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22046231$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://pasteur.hal.science/pasteur-02093194$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Hill, Marcelo</creatorcontrib><creatorcontrib>Deghmane, Ala-Eddine</creatorcontrib><creatorcontrib>Segovia, Mercedes</creatorcontrib><creatorcontrib>Zarantonelli, Maria Leticia</creatorcontrib><creatorcontrib>Tilly, Gaëlle</creatorcontrib><creatorcontrib>Blancou, Philippe</creatorcontrib><creatorcontrib>Bériou, Gaëlle</creatorcontrib><creatorcontrib>Josien, Régis</creatorcontrib><creatorcontrib>Anegon, Ignacio</creatorcontrib><creatorcontrib>Hong, Eva</creatorcontrib><creatorcontrib>Ruckly, Corinne</creatorcontrib><creatorcontrib>Antignac, Aude</creatorcontrib><creatorcontrib>El Ghachi, Meriem</creatorcontrib><creatorcontrib>Boneca, Ivo Gomperts</creatorcontrib><creatorcontrib>Taha, Muhamed-Kheir</creatorcontrib><creatorcontrib>Cuturi, Maria Cristina</creatorcontrib><title>Penicillin binding proteins as danger signals: meningococcal penicillin binding protein 2 activates dendritic cells through Toll-like receptor 4</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Neisseria meningitidis is a human pathogen responsible for life-threatening inflammatory diseases. Meningococcal penicillin-binding proteins (PBPs) and particularly PBP2 are involved in bacterial resistance to β-lactams. Here we describe a novel function for PBP2 that activates human and mouse dendritic cells (DC) in a time and dose-dependent manner. PBP2 induces MHC II (LOGEC50 = 4.7 µg/ml ± 0.1), CD80 (LOGEC50 = 4.88 µg/ml ± 0.15) and CD86 (LOGEC50 = 5.36 µg/ml ± 0.1). This effect was abolished when DCs were co-treated with anti-PBP2 antibodies. PBP2-treated DCs displayed enhanced immunogenic properties in vitro and in vivo. Furthermore, proteins co-purified with PBP2 showed no effect on DC maturation. We show through different in vivo and in vitro approaches that this effect is not due to endotoxin contamination. At the mechanistic level, PBP2 induces nuclear localization of p65 NF-kB of 70.7 ± 5.1% cells versus 12 ± 2.6% in untreated DCs and needs TLR4 expression to mature DCs. Immunoprecipitation and blocking experiments showed thatPBP2 binds TLR4. In conclusion, we describe a novel function of meningococcal PBP2 as a pathogen associated molecular pattern (PAMP) at the host-pathogen interface that could be recognized by the immune system as a danger signal, promoting the development of immune responses.</description><subject>Animals</subject><subject>Antibiotics</subject><subject>Antibodies</subject><subject>B cells</subject><subject>B7-1 Antigen</subject><subject>B7-1 Antigen - biosynthesis</subject><subject>B7-2 Antigen</subject><subject>B7-2 Antigen - biosynthesis</subject><subject>Bacteria</subject><subject>Bacterial infections</subject><subject>Bacteriology</subject><subject>Binding</subject><subject>Binding proteins</subject><subject>Biology</subject><subject>CD80 antigen</subject><subject>CD86 antigen</subject><subject>Cells, Cultured</subject><subject>Contamination</subject><subject>Dendritic Cells</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - microbiology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug resistance</subject><subject>Hazards</subject><subject>Histocompatibility Antigens Class II</subject><subject>Histocompatibility Antigens Class II - biosynthesis</subject><subject>Host-Pathogen Interactions</subject><subject>Host-Pathogen Interactions - immunology</subject><subject>Human behavior</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunogenicity</subject><subject>Immunoprecipitation</subject><subject>Inflammatory diseases</subject><subject>Lactams</subject><subject>Life Sciences</subject><subject>Localization</subject><subject>Major histocompatibility complex</subject><subject>Maturation</subject><subject>Medicine</subject><subject>Mice</subject><subject>Microbiology and Parasitology</subject><subject>Neisseria meningitidis</subject><subject>Neisseria meningitidis - chemistry</subject><subject>Neisseria meningitidis - immunology</subject><subject>NF-κB protein</subject><subject>Pathogens</subject><subject>Pattern recognition</subject><subject>Penicillin</subject><subject>Penicillin-Binding Proteins</subject><subject>Penicillin-Binding Proteins - pharmacology</subject><subject>Protein binding</subject><subject>Proteins</subject><subject>Rodents</subject><subject>TLR4 protein</subject><subject>Toll-Like Receptor 4</subject><subject>Toll-Like Receptor 4 - immunology</subject><subject>Toll-like receptors</subject><subject>Vaccines</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk99qFDEUxgdRbK2-gWhAELzYNf8mM_FCWIraQqGi1duQzZyZTc0mY5Ip-hY-sll3W7piQeZihjO_7_tykpyqekrwnLCGvL4MU_TazcfgYY4xZVLW96pDIhmdCYrZ_VvfB9WjlC4xrlkrxMPqgFLMBWXksPr1Ebw11jnr0dL6zvoBjTFksD4hnVCn_QARJTuUrPQGrQvuh2CCMdqh8U4xokibbK90hmICvos2W4MMOJdQXsUwDSt0EZybOfsNUAQDYw4R8cfVg74kwZPd-6j68v7dxfHJ7Oz8w-nx4mxmGirzjHBKG6yXouey7njf1E1PzZJpKRomtF6SpQDOoMe8JbI2rQbgpVL32OBaCnZUPd_6ji4ktdvMpAjDsmW4FW0hTrdEF_SlGqNd6_hTBW3Vn0KIg9KxNOVACQINrTvZNn3DBedlFVjwkkY41EY3xevtLm1arqEz4HPUbs90_4-3KzWEK8XK6RFCisFsa7D6S3ayOFOjThmmqDDFkhHJrzb8i11gDN8nSPmOFnfUoEsX1vehhJu1TUYteCPKZZFyQ83_QZWng7U15fr1ttT3BK_2BIXJ8CMPekpJnX7-9P_s-dd99uUtdgXa5VUKbso2-LQP8i1oYkgpQn-zZQSrzfRc74baTI_aTU-RPbt9Sjei63FhvwFhuBZy</recordid><startdate>20111027</startdate><enddate>20111027</enddate><creator>Hill, Marcelo</creator><creator>Deghmane, Ala-Eddine</creator><creator>Segovia, Mercedes</creator><creator>Zarantonelli, Maria Leticia</creator><creator>Tilly, Gaëlle</creator><creator>Blancou, Philippe</creator><creator>Bériou, Gaëlle</creator><creator>Josien, Régis</creator><creator>Anegon, Ignacio</creator><creator>Hong, Eva</creator><creator>Ruckly, Corinne</creator><creator>Antignac, Aude</creator><creator>El Ghachi, Meriem</creator><creator>Boneca, Ivo Gomperts</creator><creator>Taha, Muhamed-Kheir</creator><creator>Cuturi, Maria Cristina</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-5249-7467</orcidid><orcidid>https://orcid.org/0000-0002-9293-9685</orcidid><orcidid>https://orcid.org/0000-0002-0716-3174</orcidid><orcidid>https://orcid.org/0000-0003-0305-8622</orcidid><orcidid>https://orcid.org/0000-0001-8700-5645</orcidid><orcidid>https://orcid.org/0000-0003-2887-1732</orcidid><orcidid>https://orcid.org/0000-0001-8122-509X</orcidid><orcidid>https://orcid.org/0000-0001-7900-7413</orcidid><orcidid>https://orcid.org/0000-0002-1589-0320</orcidid></search><sort><creationdate>20111027</creationdate><title>Penicillin binding proteins as danger signals: meningococcal penicillin binding protein 2 activates dendritic cells through Toll-like receptor 4</title><author>Hill, Marcelo ; Deghmane, Ala-Eddine ; Segovia, Mercedes ; Zarantonelli, Maria Leticia ; Tilly, Gaëlle ; Blancou, Philippe ; Bériou, Gaëlle ; Josien, Régis ; Anegon, Ignacio ; Hong, Eva ; Ruckly, Corinne ; Antignac, Aude ; El Ghachi, Meriem ; Boneca, Ivo Gomperts ; Taha, Muhamed-Kheir ; Cuturi, Maria Cristina</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c729t-142270ab6f495d4f757f2cb3a96736aab1b6e43ef048195c8aee46e45f0c05963</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Antibiotics</topic><topic>Antibodies</topic><topic>B cells</topic><topic>B7-1 Antigen</topic><topic>B7-1 Antigen - biosynthesis</topic><topic>B7-2 Antigen</topic><topic>B7-2 Antigen - biosynthesis</topic><topic>Bacteria</topic><topic>Bacterial infections</topic><topic>Bacteriology</topic><topic>Binding</topic><topic>Binding proteins</topic><topic>Biology</topic><topic>CD80 antigen</topic><topic>CD86 antigen</topic><topic>Cells, Cultured</topic><topic>Contamination</topic><topic>Dendritic Cells</topic><topic>Dendritic Cells - immunology</topic><topic>Dendritic Cells - microbiology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug resistance</topic><topic>Hazards</topic><topic>Histocompatibility Antigens Class II</topic><topic>Histocompatibility Antigens Class II - biosynthesis</topic><topic>Host-Pathogen Interactions</topic><topic>Host-Pathogen Interactions - immunology</topic><topic>Human behavior</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immune system</topic><topic>Immunogenicity</topic><topic>Immunoprecipitation</topic><topic>Inflammatory diseases</topic><topic>Lactams</topic><topic>Life Sciences</topic><topic>Localization</topic><topic>Major histocompatibility complex</topic><topic>Maturation</topic><topic>Medicine</topic><topic>Mice</topic><topic>Microbiology and Parasitology</topic><topic>Neisseria meningitidis</topic><topic>Neisseria meningitidis - chemistry</topic><topic>Neisseria meningitidis - immunology</topic><topic>NF-κB protein</topic><topic>Pathogens</topic><topic>Pattern recognition</topic><topic>Penicillin</topic><topic>Penicillin-Binding Proteins</topic><topic>Penicillin-Binding Proteins - pharmacology</topic><topic>Protein binding</topic><topic>Proteins</topic><topic>Rodents</topic><topic>TLR4 protein</topic><topic>Toll-Like Receptor 4</topic><topic>Toll-Like Receptor 4 - immunology</topic><topic>Toll-like receptors</topic><topic>Vaccines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hill, Marcelo</creatorcontrib><creatorcontrib>Deghmane, Ala-Eddine</creatorcontrib><creatorcontrib>Segovia, Mercedes</creatorcontrib><creatorcontrib>Zarantonelli, Maria Leticia</creatorcontrib><creatorcontrib>Tilly, Gaëlle</creatorcontrib><creatorcontrib>Blancou, Philippe</creatorcontrib><creatorcontrib>Bériou, Gaëlle</creatorcontrib><creatorcontrib>Josien, Régis</creatorcontrib><creatorcontrib>Anegon, Ignacio</creatorcontrib><creatorcontrib>Hong, Eva</creatorcontrib><creatorcontrib>Ruckly, Corinne</creatorcontrib><creatorcontrib>Antignac, Aude</creatorcontrib><creatorcontrib>El Ghachi, Meriem</creatorcontrib><creatorcontrib>Boneca, Ivo Gomperts</creatorcontrib><creatorcontrib>Taha, Muhamed-Kheir</creatorcontrib><creatorcontrib>Cuturi, Maria Cristina</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hill, Marcelo</au><au>Deghmane, Ala-Eddine</au><au>Segovia, Mercedes</au><au>Zarantonelli, Maria Leticia</au><au>Tilly, Gaëlle</au><au>Blancou, Philippe</au><au>Bériou, Gaëlle</au><au>Josien, Régis</au><au>Anegon, Ignacio</au><au>Hong, Eva</au><au>Ruckly, Corinne</au><au>Antignac, Aude</au><au>El Ghachi, Meriem</au><au>Boneca, Ivo Gomperts</au><au>Taha, Muhamed-Kheir</au><au>Cuturi, Maria Cristina</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Penicillin binding proteins as danger signals: meningococcal penicillin binding protein 2 activates dendritic cells through Toll-like receptor 4</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2011-10-27</date><risdate>2011</risdate><volume>6</volume><issue>10</issue><spage>e23995</spage><pages>e23995-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Neisseria meningitidis is a human pathogen responsible for life-threatening inflammatory diseases. Meningococcal penicillin-binding proteins (PBPs) and particularly PBP2 are involved in bacterial resistance to β-lactams. Here we describe a novel function for PBP2 that activates human and mouse dendritic cells (DC) in a time and dose-dependent manner. PBP2 induces MHC II (LOGEC50 = 4.7 µg/ml ± 0.1), CD80 (LOGEC50 = 4.88 µg/ml ± 0.15) and CD86 (LOGEC50 = 5.36 µg/ml ± 0.1). This effect was abolished when DCs were co-treated with anti-PBP2 antibodies. PBP2-treated DCs displayed enhanced immunogenic properties in vitro and in vivo. Furthermore, proteins co-purified with PBP2 showed no effect on DC maturation. We show through different in vivo and in vitro approaches that this effect is not due to endotoxin contamination. At the mechanistic level, PBP2 induces nuclear localization of p65 NF-kB of 70.7 ± 5.1% cells versus 12 ± 2.6% in untreated DCs and needs TLR4 expression to mature DCs. Immunoprecipitation and blocking experiments showed thatPBP2 binds TLR4. In conclusion, we describe a novel function of meningococcal PBP2 as a pathogen associated molecular pattern (PAMP) at the host-pathogen interface that could be recognized by the immune system as a danger signal, promoting the development of immune responses.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22046231</pmid><doi>10.1371/journal.pone.0023995</doi><tpages>e23995</tpages><orcidid>https://orcid.org/0000-0001-5249-7467</orcidid><orcidid>https://orcid.org/0000-0002-9293-9685</orcidid><orcidid>https://orcid.org/0000-0002-0716-3174</orcidid><orcidid>https://orcid.org/0000-0003-0305-8622</orcidid><orcidid>https://orcid.org/0000-0001-8700-5645</orcidid><orcidid>https://orcid.org/0000-0003-2887-1732</orcidid><orcidid>https://orcid.org/0000-0001-8122-509X</orcidid><orcidid>https://orcid.org/0000-0001-7900-7413</orcidid><orcidid>https://orcid.org/0000-0002-1589-0320</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2011-10, Vol.6 (10), p.e23995 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1309830868 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Animals Antibiotics Antibodies B cells B7-1 Antigen B7-1 Antigen - biosynthesis B7-2 Antigen B7-2 Antigen - biosynthesis Bacteria Bacterial infections Bacteriology Binding Binding proteins Biology CD80 antigen CD86 antigen Cells, Cultured Contamination Dendritic Cells Dendritic Cells - immunology Dendritic Cells - microbiology Dose-Response Relationship, Drug Drug resistance Hazards Histocompatibility Antigens Class II Histocompatibility Antigens Class II - biosynthesis Host-Pathogen Interactions Host-Pathogen Interactions - immunology Human behavior Humans Immune response Immune system Immunogenicity Immunoprecipitation Inflammatory diseases Lactams Life Sciences Localization Major histocompatibility complex Maturation Medicine Mice Microbiology and Parasitology Neisseria meningitidis Neisseria meningitidis - chemistry Neisseria meningitidis - immunology NF-κB protein Pathogens Pattern recognition Penicillin Penicillin-Binding Proteins Penicillin-Binding Proteins - pharmacology Protein binding Proteins Rodents TLR4 protein Toll-Like Receptor 4 Toll-Like Receptor 4 - immunology Toll-like receptors Vaccines |
| title | Penicillin binding proteins as danger signals: meningococcal penicillin binding protein 2 activates dendritic cells through Toll-like receptor 4 |
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