Neisserial Outer Membrane Vesicles Bind the Coinhibitory Receptor Carcinoembryonic Antigen-Related Cellular Adhesion Molecule 1 and Suppress CD4⁺ T Lymphocyte Function
Pathogenic Neisseria bacteria naturally liberate outer membrane "blebs," which are presumed to contribute to pathology, and the detergent-extracted outer membrane vesicles (OMVs) from Neisseria meningitidis are currently employed as meningococcal vaccines in humans. While the composition o...
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description | Pathogenic Neisseria bacteria naturally liberate outer membrane "blebs," which are presumed to contribute to pathology, and the detergent-extracted outer membrane vesicles (OMVs) from Neisseria meningitidis are currently employed as meningococcal vaccines in humans. While the composition of these vesicles reflects the bacteria from which they are derived, the functions of many of their constituent proteins remain unexplored. The neisserial colony opacity-associated Opa proteins function as adhesins, the majority of which mediate bacterial attachment to human carcinoembryonic antigen-related cellular adhesion molecules (CEACAMs). Herein, we demonstrate that the Opa proteins within OMV preparations retain the capacity to bind the immunoreceptor tyrosine-based inhibitory motif-containing coinhibitory receptor CEACAM1. When CD4⁺ T lymphocytes were exposed to OMVs from Opa-expressing bacteria, their activation and proliferation in response to a variety of stimuli were effectively halted. This potent immunosuppressive effect suggests that localized infection will generate a "zone of inhibition" resulting from the diffusion of membrane blebs into the surrounding tissues. Moreover, it demonstrates that OMV-based vaccines must be developed from strains that lack CEACAM1-binding Opa variants. |
doi_str_mv | 10.1128/IAI.00222-07 |
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While the composition of these vesicles reflects the bacteria from which they are derived, the functions of many of their constituent proteins remain unexplored. The neisserial colony opacity-associated Opa proteins function as adhesins, the majority of which mediate bacterial attachment to human carcinoembryonic antigen-related cellular adhesion molecules (CEACAMs). Herein, we demonstrate that the Opa proteins within OMV preparations retain the capacity to bind the immunoreceptor tyrosine-based inhibitory motif-containing coinhibitory receptor CEACAM1. When CD4⁺ T lymphocytes were exposed to OMVs from Opa-expressing bacteria, their activation and proliferation in response to a variety of stimuli were effectively halted. This potent immunosuppressive effect suggests that localized infection will generate a "zone of inhibition" resulting from the diffusion of membrane blebs into the surrounding tissues. Moreover, it demonstrates that OMV-based vaccines must be developed from strains that lack CEACAM1-binding Opa variants.</description><identifier>ISSN: 0019-9567</identifier><identifier>EISSN: 1098-5522</identifier><identifier>DOI: 10.1128/IAI.00222-07</identifier><identifier>PMID: 17620353</identifier><identifier>CODEN: INFIBR</identifier><language>eng</language><publisher>Washington, DC: American Society for Microbiology</publisher><subject>Amino Acid Motifs - immunology ; Antigens, CD - metabolism ; Antigens, CD - physiology ; Bacterial Adhesion ; Bacterial Outer Membrane Proteins - metabolism ; Bacterial Outer Membrane Proteins - physiology ; Bacteriology ; Biological and medical sciences ; CD4-Positive T-Lymphocytes - cytology ; CD4-Positive T-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - metabolism ; Cell Adhesion Molecules - metabolism ; Cell Adhesion Molecules - physiology ; Cell Wall - physiology ; Cells, Cultured ; Fundamental and applied biological sciences. Psychology ; Growth Inhibitors - metabolism ; Growth Inhibitors - physiology ; Host Response and Inflammation ; Humans ; Immunosuppression ; Jurkat Cells ; Microbiology ; Neisseria lactamica - immunology ; Neisseria meningitidis - immunology ; Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains ; Receptors, Immunologic - metabolism ; Receptors, Immunologic - physiology ; Tyrosine - metabolism</subject><ispartof>Infection and Immunity, 2007-09, Vol.75 (9), p.4449-4455</ispartof><rights>2008 INIST-CNRS</rights><rights>Copyright © 2007, American Society for Microbiology 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c505t-4c50ce06340369f9c16c8d1b8ad531d4c79cdf6637765a1821b88fa918c766a3</citedby><cites>FETCH-LOGICAL-c505t-4c50ce06340369f9c16c8d1b8ad531d4c79cdf6637765a1821b88fa918c766a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1951172/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1951172/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,3175,3176,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19018962$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17620353$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Hannah S.W</creatorcontrib><creatorcontrib>Boulton, Ian C</creatorcontrib><creatorcontrib>Reddin, Karen</creatorcontrib><creatorcontrib>Wong, Henry</creatorcontrib><creatorcontrib>Halliwell, Denise</creatorcontrib><creatorcontrib>Mandelboim, Ofer</creatorcontrib><creatorcontrib>Gorringe, Andrew R</creatorcontrib><creatorcontrib>Gray-Owen, Scott D</creatorcontrib><title>Neisserial Outer Membrane Vesicles Bind the Coinhibitory Receptor Carcinoembryonic Antigen-Related Cellular Adhesion Molecule 1 and Suppress CD4⁺ T Lymphocyte Function</title><title>Infection and Immunity</title><addtitle>Infect Immun</addtitle><description>Pathogenic Neisseria bacteria naturally liberate outer membrane "blebs," which are presumed to contribute to pathology, and the detergent-extracted outer membrane vesicles (OMVs) from Neisseria meningitidis are currently employed as meningococcal vaccines in humans. While the composition of these vesicles reflects the bacteria from which they are derived, the functions of many of their constituent proteins remain unexplored. The neisserial colony opacity-associated Opa proteins function as adhesins, the majority of which mediate bacterial attachment to human carcinoembryonic antigen-related cellular adhesion molecules (CEACAMs). Herein, we demonstrate that the Opa proteins within OMV preparations retain the capacity to bind the immunoreceptor tyrosine-based inhibitory motif-containing coinhibitory receptor CEACAM1. When CD4⁺ T lymphocytes were exposed to OMVs from Opa-expressing bacteria, their activation and proliferation in response to a variety of stimuli were effectively halted. This potent immunosuppressive effect suggests that localized infection will generate a "zone of inhibition" resulting from the diffusion of membrane blebs into the surrounding tissues. Moreover, it demonstrates that OMV-based vaccines must be developed from strains that lack CEACAM1-binding Opa variants.</description><subject>Amino Acid Motifs - immunology</subject><subject>Antigens, CD - metabolism</subject><subject>Antigens, CD - physiology</subject><subject>Bacterial Adhesion</subject><subject>Bacterial Outer Membrane Proteins - metabolism</subject><subject>Bacterial Outer Membrane Proteins - physiology</subject><subject>Bacteriology</subject><subject>Biological and medical sciences</subject><subject>CD4-Positive T-Lymphocytes - cytology</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>Cell Adhesion Molecules - metabolism</subject><subject>Cell Adhesion Molecules - physiology</subject><subject>Cell Wall - physiology</subject><subject>Cells, Cultured</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Growth Inhibitors - metabolism</subject><subject>Growth Inhibitors - physiology</subject><subject>Host Response and Inflammation</subject><subject>Humans</subject><subject>Immunosuppression</subject><subject>Jurkat Cells</subject><subject>Microbiology</subject><subject>Neisseria lactamica - immunology</subject><subject>Neisseria meningitidis - immunology</subject><subject>Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains</subject><subject>Receptors, Immunologic - metabolism</subject><subject>Receptors, Immunologic - physiology</subject><subject>Tyrosine - metabolism</subject><issn>0019-9567</issn><issn>1098-5522</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVks1u1DAQxyMEokvhxhnMAU6k2Pnwx6XSEiistKVSu3C1vM5kY5TYwU5AOfI4vAKPw5PgZVcUTmNrfvOf8fydJI8JPiMk469Wy9UZxlmWpZjdSRYEC56WZZbdTRYYE5GKkrKT5EEIn-O1KAp-PzkhjGY4L_NF8uMDmBDAG9Whq2kEjy6h33plAX2CYHQHAb02tkZjC6hyxrZma0bnZ3QNGoZ4QpXy2li3L5udNRot7Wh2YNNr6NQINaqg66ZOebSs26jpLLp0HeipA0SQito30zB4CAFVb4pf33-iDVrP_dA6PY-ALiarx1j0MLnXqC7Ao2M8TTYXbzfV-3R99W5VLdepLnE5pkUMGjDNC5xT0QhNqOY12XJVlzmpC82ErhtKc8ZoqQjPYoo3ShCuGaUqP03OD7LDtO2h1mBHrzo5eNMrP0unjPw_Y00rd-6rJKIkhGVR4MVRwLsvE4RR9ibouIK4UzcFSTnhsbmI4MsDqL0LwUPztwnBcm-tjNbKP9ZKzCL-5N_BbuGjlxF4fgRU0KproonahFtOYMIF3Q_47MC1Ztd-Mx6kCr008WGslELGL7Kf7emBaZSTauejzsebDJMcYyY4JzT_DfkNxG8</recordid><startdate>20070901</startdate><enddate>20070901</enddate><creator>Lee, Hannah S.W</creator><creator>Boulton, Ian C</creator><creator>Reddin, Karen</creator><creator>Wong, Henry</creator><creator>Halliwell, Denise</creator><creator>Mandelboim, Ofer</creator><creator>Gorringe, Andrew R</creator><creator>Gray-Owen, Scott D</creator><general>American Society for Microbiology</general><scope>FBQ</scope><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>5PM</scope></search><sort><creationdate>20070901</creationdate><title>Neisserial Outer Membrane Vesicles Bind the Coinhibitory Receptor Carcinoembryonic Antigen-Related Cellular Adhesion Molecule 1 and Suppress CD4⁺ T Lymphocyte Function</title><author>Lee, Hannah S.W ; Boulton, Ian C ; Reddin, Karen ; Wong, Henry ; Halliwell, Denise ; Mandelboim, Ofer ; Gorringe, Andrew R ; Gray-Owen, Scott D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c505t-4c50ce06340369f9c16c8d1b8ad531d4c79cdf6637765a1821b88fa918c766a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Amino Acid Motifs - immunology</topic><topic>Antigens, CD - metabolism</topic><topic>Antigens, CD - physiology</topic><topic>Bacterial Adhesion</topic><topic>Bacterial Outer Membrane Proteins - metabolism</topic><topic>Bacterial Outer Membrane Proteins - physiology</topic><topic>Bacteriology</topic><topic>Biological and medical sciences</topic><topic>CD4-Positive T-Lymphocytes - cytology</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>CD4-Positive T-Lymphocytes - metabolism</topic><topic>Cell Adhesion Molecules - metabolism</topic><topic>Cell Adhesion Molecules - physiology</topic><topic>Cell Wall - physiology</topic><topic>Cells, Cultured</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Growth Inhibitors - metabolism</topic><topic>Growth Inhibitors - physiology</topic><topic>Host Response and Inflammation</topic><topic>Humans</topic><topic>Immunosuppression</topic><topic>Jurkat Cells</topic><topic>Microbiology</topic><topic>Neisseria lactamica - immunology</topic><topic>Neisseria meningitidis - immunology</topic><topic>Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains</topic><topic>Receptors, Immunologic - metabolism</topic><topic>Receptors, Immunologic - physiology</topic><topic>Tyrosine - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Hannah S.W</creatorcontrib><creatorcontrib>Boulton, Ian C</creatorcontrib><creatorcontrib>Reddin, Karen</creatorcontrib><creatorcontrib>Wong, Henry</creatorcontrib><creatorcontrib>Halliwell, Denise</creatorcontrib><creatorcontrib>Mandelboim, Ofer</creatorcontrib><creatorcontrib>Gorringe, Andrew R</creatorcontrib><creatorcontrib>Gray-Owen, Scott D</creatorcontrib><collection>AGRIS</collection><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>PubMed Central (Full Participant titles)</collection><jtitle>Infection and Immunity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Hannah S.W</au><au>Boulton, Ian C</au><au>Reddin, Karen</au><au>Wong, Henry</au><au>Halliwell, Denise</au><au>Mandelboim, Ofer</au><au>Gorringe, Andrew R</au><au>Gray-Owen, Scott D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neisserial Outer Membrane Vesicles Bind the Coinhibitory Receptor Carcinoembryonic Antigen-Related Cellular Adhesion Molecule 1 and Suppress CD4⁺ T Lymphocyte Function</atitle><jtitle>Infection and Immunity</jtitle><addtitle>Infect Immun</addtitle><date>2007-09-01</date><risdate>2007</risdate><volume>75</volume><issue>9</issue><spage>4449</spage><epage>4455</epage><pages>4449-4455</pages><issn>0019-9567</issn><eissn>1098-5522</eissn><coden>INFIBR</coden><abstract>Pathogenic Neisseria bacteria naturally liberate outer membrane "blebs," which are presumed to contribute to pathology, and the detergent-extracted outer membrane vesicles (OMVs) from Neisseria meningitidis are currently employed as meningococcal vaccines in humans. While the composition of these vesicles reflects the bacteria from which they are derived, the functions of many of their constituent proteins remain unexplored. The neisserial colony opacity-associated Opa proteins function as adhesins, the majority of which mediate bacterial attachment to human carcinoembryonic antigen-related cellular adhesion molecules (CEACAMs). Herein, we demonstrate that the Opa proteins within OMV preparations retain the capacity to bind the immunoreceptor tyrosine-based inhibitory motif-containing coinhibitory receptor CEACAM1. When CD4⁺ T lymphocytes were exposed to OMVs from Opa-expressing bacteria, their activation and proliferation in response to a variety of stimuli were effectively halted. This potent immunosuppressive effect suggests that localized infection will generate a "zone of inhibition" resulting from the diffusion of membrane blebs into the surrounding tissues. Moreover, it demonstrates that OMV-based vaccines must be developed from strains that lack CEACAM1-binding Opa variants.</abstract><cop>Washington, DC</cop><pub>American Society for Microbiology</pub><pmid>17620353</pmid><doi>10.1128/IAI.00222-07</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Amino Acid Motifs - immunology Antigens, CD - metabolism Antigens, CD - physiology Bacterial Adhesion Bacterial Outer Membrane Proteins - metabolism Bacterial Outer Membrane Proteins - physiology Bacteriology Biological and medical sciences CD4-Positive T-Lymphocytes - cytology CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism Cell Adhesion Molecules - metabolism Cell Adhesion Molecules - physiology Cell Wall - physiology Cells, Cultured Fundamental and applied biological sciences. Psychology Growth Inhibitors - metabolism Growth Inhibitors - physiology Host Response and Inflammation Humans Immunosuppression Jurkat Cells Microbiology Neisseria lactamica - immunology Neisseria meningitidis - immunology Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains Receptors, Immunologic - metabolism Receptors, Immunologic - physiology Tyrosine - metabolism |
title | Neisserial Outer Membrane Vesicles Bind the Coinhibitory Receptor Carcinoembryonic Antigen-Related Cellular Adhesion Molecule 1 and Suppress CD4⁺ T Lymphocyte Function |
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