Dendritic Cell Stimulation by Mycobacterial Hsp70 Is Mediated Through CCR5
An effective host immune response to mycobacterial infection must control pathogen dissemination without inducing immunopathology. Constitutive overexpression of mycobacterial heat shock protein (myHsp70) is associated with impaired bacterial persistence, but the immune-mediated mechanisms are unkno...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2006-10, Vol.314 (5798), p.454-458 |
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| creator | Floto, R. Andres MacAry, Paul A Boname, Jessica M Mien, Tan Suet Kampmann, Beate Hair, James R Huey, Oh Seen Houben, Edith N.G Pieters, Jean Day, Cheryl Oehlmann, Wulf Singh, Mahavir Smith, Kenneth G.C Lehner, Paul J |
| description | An effective host immune response to mycobacterial infection must control pathogen dissemination without inducing immunopathology. Constitutive overexpression of mycobacterial heat shock protein (myHsp70) is associated with impaired bacterial persistence, but the immune-mediated mechanisms are unknown. We found that myHsp70, in addition to enhancing antigen delivery to human dendritic cells, signaled through the CCR5 chemokine receptor, promoting dendritic cell aggregation, immune synapse formation between dendritic cells and T cells, and the generation of effector immune responses. Thus, CCR5 acts as a pattern-recognition receptor for myHsp70, which may have implications for both the pathophysiology of tuberculosis and the use of myHsps in tumor-directed immunotherapy. |
| doi_str_mv | 10.1126/science.1133515 |
| format | Article |
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Andres ; MacAry, Paul A ; Boname, Jessica M ; Mien, Tan Suet ; Kampmann, Beate ; Hair, James R ; Huey, Oh Seen ; Houben, Edith N.G ; Pieters, Jean ; Day, Cheryl ; Oehlmann, Wulf ; Singh, Mahavir ; Smith, Kenneth G.C ; Lehner, Paul J</creator><creatorcontrib>Floto, R. Andres ; MacAry, Paul A ; Boname, Jessica M ; Mien, Tan Suet ; Kampmann, Beate ; Hair, James R ; Huey, Oh Seen ; Houben, Edith N.G ; Pieters, Jean ; Day, Cheryl ; Oehlmann, Wulf ; Singh, Mahavir ; Smith, Kenneth G.C ; Lehner, Paul J</creatorcontrib><description>An effective host immune response to mycobacterial infection must control pathogen dissemination without inducing immunopathology. Constitutive overexpression of mycobacterial heat shock protein (myHsp70) is associated with impaired bacterial persistence, but the immune-mediated mechanisms are unknown. We found that myHsp70, in addition to enhancing antigen delivery to human dendritic cells, signaled through the CCR5 chemokine receptor, promoting dendritic cell aggregation, immune synapse formation between dendritic cells and T cells, and the generation of effector immune responses. Thus, CCR5 acts as a pattern-recognition receptor for myHsp70, which may have implications for both the pathophysiology of tuberculosis and the use of myHsps in tumor-directed immunotherapy.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1133515</identifier><identifier>PMID: 17053144</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: American Association for the Advancement of Science</publisher><subject>Aggregation ; Antigens ; Bacteria ; Bacterial Proteins - immunology ; Bacterial Proteins - physiology ; Biological and medical sciences ; Calcium ; Calcium Signaling ; Cell Adhesion Molecules - metabolism ; Cell Aggregation ; Cell Line, Tumor ; Cell Membrane - ultrastructure ; Cell membranes ; Cell Movement ; Cell physiology ; Dendritic cells ; Dendritic Cells - immunology ; Dendritic Cells - physiology ; Dendritic Cells - ultrastructure ; Fundamental and applied biological sciences. Psychology ; HSP70 Heat-Shock Proteins - immunology ; HSP70 Heat-Shock Proteins - physiology ; Humans ; Immune system ; Immunology ; Infections ; Interleukin-6 - metabolism ; Molecular and cellular biology ; Mycobacterium ; Mycobacterium bovis - immunology ; Mycobacterium bovis - physiology ; Mycobacterium tuberculosis ; Proteins ; Pseudopodia - ultrastructure ; Receptors ; Receptors, CCR5 - genetics ; Receptors, CCR5 - physiology ; Signal transduction ; Synapses ; T lymphocytes ; T-Lymphocytes - immunology ; T-Lymphocytes - physiology ; T-Lymphocytes, Cytotoxic - immunology ; Toxins ; Whooping cough</subject><ispartof>Science (American Association for the Advancement of Science), 2006-10, Vol.314 (5798), p.454-458</ispartof><rights>Copyright 2006 American Association for the Advancement of Science</rights><rights>2007 INIST-CNRS</rights><rights>Copyright American Association for the Advancement of Science Oct 20, 2006</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c587t-2f857633f38bca940c844574e4ddc7eacd65ee605a34e7cfc98090809d88f9493</citedby><cites>FETCH-LOGICAL-c587t-2f857633f38bca940c844574e4ddc7eacd65ee605a34e7cfc98090809d88f9493</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/20031582$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/20031582$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,776,780,799,2871,2872,27901,27902,57992,58225</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18236555$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17053144$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Floto, R. Andres</creatorcontrib><creatorcontrib>MacAry, Paul A</creatorcontrib><creatorcontrib>Boname, Jessica M</creatorcontrib><creatorcontrib>Mien, Tan Suet</creatorcontrib><creatorcontrib>Kampmann, Beate</creatorcontrib><creatorcontrib>Hair, James R</creatorcontrib><creatorcontrib>Huey, Oh Seen</creatorcontrib><creatorcontrib>Houben, Edith N.G</creatorcontrib><creatorcontrib>Pieters, Jean</creatorcontrib><creatorcontrib>Day, Cheryl</creatorcontrib><creatorcontrib>Oehlmann, Wulf</creatorcontrib><creatorcontrib>Singh, Mahavir</creatorcontrib><creatorcontrib>Smith, Kenneth G.C</creatorcontrib><creatorcontrib>Lehner, Paul J</creatorcontrib><title>Dendritic Cell Stimulation by Mycobacterial Hsp70 Is Mediated Through CCR5</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>An effective host immune response to mycobacterial infection must control pathogen dissemination without inducing immunopathology. Constitutive overexpression of mycobacterial heat shock protein (myHsp70) is associated with impaired bacterial persistence, but the immune-mediated mechanisms are unknown. We found that myHsp70, in addition to enhancing antigen delivery to human dendritic cells, signaled through the CCR5 chemokine receptor, promoting dendritic cell aggregation, immune synapse formation between dendritic cells and T cells, and the generation of effector immune responses. Thus, CCR5 acts as a pattern-recognition receptor for myHsp70, which may have implications for both the pathophysiology of tuberculosis and the use of myHsps in tumor-directed immunotherapy.</description><subject>Aggregation</subject><subject>Antigens</subject><subject>Bacteria</subject><subject>Bacterial Proteins - immunology</subject><subject>Bacterial Proteins - physiology</subject><subject>Biological and medical sciences</subject><subject>Calcium</subject><subject>Calcium Signaling</subject><subject>Cell Adhesion Molecules - metabolism</subject><subject>Cell Aggregation</subject><subject>Cell Line, Tumor</subject><subject>Cell Membrane - ultrastructure</subject><subject>Cell membranes</subject><subject>Cell Movement</subject><subject>Cell physiology</subject><subject>Dendritic cells</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - physiology</subject><subject>Dendritic Cells - ultrastructure</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>HSP70 Heat-Shock Proteins - immunology</subject><subject>HSP70 Heat-Shock Proteins - physiology</subject><subject>Humans</subject><subject>Immune system</subject><subject>Immunology</subject><subject>Infections</subject><subject>Interleukin-6 - metabolism</subject><subject>Molecular and cellular biology</subject><subject>Mycobacterium</subject><subject>Mycobacterium bovis - immunology</subject><subject>Mycobacterium bovis - physiology</subject><subject>Mycobacterium tuberculosis</subject><subject>Proteins</subject><subject>Pseudopodia - ultrastructure</subject><subject>Receptors</subject><subject>Receptors, CCR5 - genetics</subject><subject>Receptors, CCR5 - physiology</subject><subject>Signal transduction</subject><subject>Synapses</subject><subject>T lymphocytes</subject><subject>T-Lymphocytes - immunology</subject><subject>T-Lymphocytes - physiology</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>Toxins</subject><subject>Whooping cough</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk1r3DAQhkVpabbbnntqKwrtzcnIo89jcT-SkFBokrPRynKixWtvJPuw_z5a1jSQyx6EEPPoQTOvCPnI4JSxUp4lF3zvfD4gCiZekQUDIwpTAr4mCwCUhQYlTsi7lNYAuWbwLTlhCgQyzhfk8qfvmxjG4Gjlu47ejGEzdXYMQ09XO3q9c8PKutHHYDt6nrYK6EWi174JdvQNvX2Iw3T_QKvqn3hP3rS2S_7DvC_J3e9ft9V5cfX3z0X146pwQquxKFstlERsUa-cNRyc5lwo7nnTOOWta6TwXoKwyL1yrTMaDOTVaN0abnBJvh-82zg8Tj6N9SYklx9vez9MqZY631CcHQXzxNBI1EfBkpWwH9hRkBkupczOJfn6AlwPU-zzWLIMheZY7m1nB8jFIaXo23obw8bGXc2g3sdbz_HWc7z5xudZO602vnnm5zwz8G0GbHK2a6PtXUjPnC5RCrEXfTpw6zQO8X89t4lMZGhJvhzqrR1qex-z4-6mBIbA8gdTucMnC-y99A</recordid><startdate>20061020</startdate><enddate>20061020</enddate><creator>Floto, R. 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Psychology</topic><topic>HSP70 Heat-Shock Proteins - immunology</topic><topic>HSP70 Heat-Shock Proteins - physiology</topic><topic>Humans</topic><topic>Immune system</topic><topic>Immunology</topic><topic>Infections</topic><topic>Interleukin-6 - metabolism</topic><topic>Molecular and cellular biology</topic><topic>Mycobacterium</topic><topic>Mycobacterium bovis - immunology</topic><topic>Mycobacterium bovis - physiology</topic><topic>Mycobacterium tuberculosis</topic><topic>Proteins</topic><topic>Pseudopodia - ultrastructure</topic><topic>Receptors</topic><topic>Receptors, CCR5 - genetics</topic><topic>Receptors, CCR5 - physiology</topic><topic>Signal transduction</topic><topic>Synapses</topic><topic>T lymphocytes</topic><topic>T-Lymphocytes - immunology</topic><topic>T-Lymphocytes - physiology</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><topic>Toxins</topic><topic>Whooping cough</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Floto, R. 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Andres</au><au>MacAry, Paul A</au><au>Boname, Jessica M</au><au>Mien, Tan Suet</au><au>Kampmann, Beate</au><au>Hair, James R</au><au>Huey, Oh Seen</au><au>Houben, Edith N.G</au><au>Pieters, Jean</au><au>Day, Cheryl</au><au>Oehlmann, Wulf</au><au>Singh, Mahavir</au><au>Smith, Kenneth G.C</au><au>Lehner, Paul J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dendritic Cell Stimulation by Mycobacterial Hsp70 Is Mediated Through CCR5</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>2006-10-20</date><risdate>2006</risdate><volume>314</volume><issue>5798</issue><spage>454</spage><epage>458</epage><pages>454-458</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><coden>SCIEAS</coden><abstract>An effective host immune response to mycobacterial infection must control pathogen dissemination without inducing immunopathology. Constitutive overexpression of mycobacterial heat shock protein (myHsp70) is associated with impaired bacterial persistence, but the immune-mediated mechanisms are unknown. We found that myHsp70, in addition to enhancing antigen delivery to human dendritic cells, signaled through the CCR5 chemokine receptor, promoting dendritic cell aggregation, immune synapse formation between dendritic cells and T cells, and the generation of effector immune responses. Thus, CCR5 acts as a pattern-recognition receptor for myHsp70, which may have implications for both the pathophysiology of tuberculosis and the use of myHsps in tumor-directed immunotherapy.</abstract><cop>Washington, DC</cop><pub>American Association for the Advancement of Science</pub><pmid>17053144</pmid><doi>10.1126/science.1133515</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 2006-10, Vol.314 (5798), p.454-458 |
| issn | 0036-8075 1095-9203 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_68980741 |
| source | American Association for the Advancement of Science; Jstor Complete Legacy; MEDLINE |
| subjects | Aggregation Antigens Bacteria Bacterial Proteins - immunology Bacterial Proteins - physiology Biological and medical sciences Calcium Calcium Signaling Cell Adhesion Molecules - metabolism Cell Aggregation Cell Line, Tumor Cell Membrane - ultrastructure Cell membranes Cell Movement Cell physiology Dendritic cells Dendritic Cells - immunology Dendritic Cells - physiology Dendritic Cells - ultrastructure Fundamental and applied biological sciences. Psychology HSP70 Heat-Shock Proteins - immunology HSP70 Heat-Shock Proteins - physiology Humans Immune system Immunology Infections Interleukin-6 - metabolism Molecular and cellular biology Mycobacterium Mycobacterium bovis - immunology Mycobacterium bovis - physiology Mycobacterium tuberculosis Proteins Pseudopodia - ultrastructure Receptors Receptors, CCR5 - genetics Receptors, CCR5 - physiology Signal transduction Synapses T lymphocytes T-Lymphocytes - immunology T-Lymphocytes - physiology T-Lymphocytes, Cytotoxic - immunology Toxins Whooping cough |
| title | Dendritic Cell Stimulation by Mycobacterial Hsp70 Is Mediated Through CCR5 |
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