Molecular mimicry of a CCR5 binding-domain in the microbial activation of dendritic cells
Toxoplasma gondii releases factors that potently stimulate production of interleukin-12 (IL-12) from dendritic cells (DCs). Purification of this activity showed that cyclophilin-18 (C-18) was its principal component, and antibodies generated against recombinant C-18 inhibited tachyzoite extract–indu...
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| Veröffentlicht in: | Nature immunology 2003-05, Vol.4 (5), p.485-490 |
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| creator | e Sousa, Caetano Reis Sher, Alan Valenzuela, Jesus G Charest, Hugues Ribeiro, Jose M Hieny, Sara Carruthers, Vern B Aliberti, Julio Andersen, John Fairlamb, Alan |
| description | Toxoplasma gondii
releases factors that potently stimulate production of interleukin-12 (IL-12) from dendritic cells (DCs). Purification of this activity showed that cyclophilin-18 (C-18) was its principal component, and antibodies generated against recombinant C-18 inhibited tachyzoite extract–induced synthesis of IL-12. Recombinant C-18 showed high affinity for and triggered cell signaling through CCR5, a chemokine receptor important in parasite-induced IL-12 production by DCs. These findings suggest that the unusual potency of
T. gondii
in inducing IL-12 from DCs results from its synthesis of a unique chemokine mimic that signals through CCR5. The ability to generate this strong protective response may benefit parasite transmission by preventing the protozoan from overwhelming its intermediate hosts. |
| doi_str_mv | 10.1038/ni915 |
| format | Article |
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releases factors that potently stimulate production of interleukin-12 (IL-12) from dendritic cells (DCs). Purification of this activity showed that cyclophilin-18 (C-18) was its principal component, and antibodies generated against recombinant C-18 inhibited tachyzoite extract–induced synthesis of IL-12. Recombinant C-18 showed high affinity for and triggered cell signaling through CCR5, a chemokine receptor important in parasite-induced IL-12 production by DCs. These findings suggest that the unusual potency of
T. gondii
in inducing IL-12 from DCs results from its synthesis of a unique chemokine mimic that signals through CCR5. The ability to generate this strong protective response may benefit parasite transmission by preventing the protozoan from overwhelming its intermediate hosts.</description><identifier>ISSN: 1529-2908</identifier><identifier>EISSN: 1529-2916</identifier><identifier>DOI: 10.1038/ni915</identifier><identifier>PMID: 12665855</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Amino Acid Sequence ; Animals ; Base Sequence ; Biomedical and Life Sciences ; Biomedicine ; Calcium Signaling ; Chemotaxis ; Cyclophilins - genetics ; Cyclophilins - immunology ; Cyclosporine - pharmacology ; Dendritic Cells - immunology ; Dendritic Cells - physiology ; DNA, Protozoan - genetics ; Immunology ; In Vitro Techniques ; Infectious Diseases ; Interleukin-12 - biosynthesis ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Molecular Mimicry ; Molecular Sequence Data ; Parasites ; Protein Structure, Tertiary ; Protozoan Proteins - genetics ; Protozoan Proteins - immunology ; Receptors, CCR5 - chemistry ; Receptors, CCR5 - deficiency ; Receptors, CCR5 - genetics ; Receptors, CCR5 - metabolism ; Recombinant Proteins - genetics ; Recombinant Proteins - immunology ; Toxoplasma - immunology ; Toxoplasma - pathogenicity</subject><ispartof>Nature immunology, 2003-05, Vol.4 (5), p.485-490</ispartof><rights>Springer Nature America, Inc. 2003</rights><rights>COPYRIGHT 2003 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group May 2003</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c523t-4c1c6705c515f38d29d744eacad9e273b5dc3c3bbdd8a983b1dfd39a0cbfd4123</citedby><cites>FETCH-LOGICAL-c523t-4c1c6705c515f38d29d744eacad9e273b5dc3c3bbdd8a983b1dfd39a0cbfd4123</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/ni915$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/ni915$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,2727,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12665855$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>e Sousa, Caetano Reis</creatorcontrib><creatorcontrib>Sher, Alan</creatorcontrib><creatorcontrib>Valenzuela, Jesus G</creatorcontrib><creatorcontrib>Charest, Hugues</creatorcontrib><creatorcontrib>Ribeiro, Jose M</creatorcontrib><creatorcontrib>Hieny, Sara</creatorcontrib><creatorcontrib>Carruthers, Vern B</creatorcontrib><creatorcontrib>Aliberti, Julio</creatorcontrib><creatorcontrib>Andersen, John</creatorcontrib><creatorcontrib>Fairlamb, Alan</creatorcontrib><title>Molecular mimicry of a CCR5 binding-domain in the microbial activation of dendritic cells</title><title>Nature immunology</title><addtitle>Nat Immunol</addtitle><addtitle>Nat Immunol</addtitle><description>Toxoplasma gondii
releases factors that potently stimulate production of interleukin-12 (IL-12) from dendritic cells (DCs). Purification of this activity showed that cyclophilin-18 (C-18) was its principal component, and antibodies generated against recombinant C-18 inhibited tachyzoite extract–induced synthesis of IL-12. Recombinant C-18 showed high affinity for and triggered cell signaling through CCR5, a chemokine receptor important in parasite-induced IL-12 production by DCs. These findings suggest that the unusual potency of
T. gondii
in inducing IL-12 from DCs results from its synthesis of a unique chemokine mimic that signals through CCR5. The ability to generate this strong protective response may benefit parasite transmission by preventing the protozoan from overwhelming its intermediate hosts.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Base Sequence</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Calcium Signaling</subject><subject>Chemotaxis</subject><subject>Cyclophilins - genetics</subject><subject>Cyclophilins - immunology</subject><subject>Cyclosporine - pharmacology</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - physiology</subject><subject>DNA, Protozoan - genetics</subject><subject>Immunology</subject><subject>In Vitro Techniques</subject><subject>Infectious Diseases</subject><subject>Interleukin-12 - biosynthesis</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Molecular Mimicry</subject><subject>Molecular Sequence Data</subject><subject>Parasites</subject><subject>Protein Structure, Tertiary</subject><subject>Protozoan Proteins - genetics</subject><subject>Protozoan Proteins - immunology</subject><subject>Receptors, CCR5 - chemistry</subject><subject>Receptors, CCR5 - deficiency</subject><subject>Receptors, CCR5 - genetics</subject><subject>Receptors, CCR5 - metabolism</subject><subject>Recombinant Proteins - genetics</subject><subject>Recombinant Proteins - immunology</subject><subject>Toxoplasma - immunology</subject><subject>Toxoplasma - pathogenicity</subject><issn>1529-2908</issn><issn>1529-2916</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkVtLHTEUhYNU1Kq_QChBaKEPo7lMZpJHOfQiKIK2Dz6FTJI5jcwkmmRK_ffNdA4e9KUQSMj-9mKtvQE4xugMI8rPvROY7YADzIioiMDNu5c34vvgfUoPCOG6beo9sI9J0zDO2AG4vw6D1dOgIhzd6HR8hqGHCq5Wtwx2zhvn15UJo3IelpN_WThToXNqgEpn91tlF_zcZKw30WWnobbDkI7Abq-GZI839yH4-fXLj9X36urm2-Xq4qrSjNBc1RrrpkVMM8x6yg0Rpq1rq7QywpKWdsxoqmnXGcOV4LTDpjdUKKS73tSY0EPwadF9jOFpsinL0aXZgfI2TEm2lBDaEvFfEHOOBBez4ukb8CFM0ZcQkhDSFtuoKdDZAq3VYKXzfcixmC62bRlQ8LZ35f-iiHLEa1qXhs-vGgqT7Z-8VlNK8vLu9jX7cWHLpFOKtpeP0Y0qPkuM5Lxu-W_dhfuwcTp1ozVbarPfbeZUSn5t4zbKW6WTBfQqT9G-KC3VvzWCuaA</recordid><startdate>20030501</startdate><enddate>20030501</enddate><creator>e Sousa, Caetano Reis</creator><creator>Sher, Alan</creator><creator>Valenzuela, Jesus G</creator><creator>Charest, Hugues</creator><creator>Ribeiro, Jose M</creator><creator>Hieny, Sara</creator><creator>Carruthers, Vern B</creator><creator>Aliberti, Julio</creator><creator>Andersen, John</creator><creator>Fairlamb, Alan</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</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>ISR</scope><scope>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</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>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20030501</creationdate><title>Molecular mimicry of a CCR5 binding-domain in the microbial activation of dendritic cells</title><author>e Sousa, Caetano Reis ; Sher, Alan ; Valenzuela, Jesus G ; Charest, Hugues ; Ribeiro, Jose M ; Hieny, Sara ; Carruthers, Vern B ; Aliberti, Julio ; Andersen, John ; Fairlamb, Alan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c523t-4c1c6705c515f38d29d744eacad9e273b5dc3c3bbdd8a983b1dfd39a0cbfd4123</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Base Sequence</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Calcium Signaling</topic><topic>Chemotaxis</topic><topic>Cyclophilins - genetics</topic><topic>Cyclophilins - immunology</topic><topic>Cyclosporine - pharmacology</topic><topic>Dendritic Cells - immunology</topic><topic>Dendritic Cells - physiology</topic><topic>DNA, Protozoan - genetics</topic><topic>Immunology</topic><topic>In Vitro Techniques</topic><topic>Infectious Diseases</topic><topic>Interleukin-12 - biosynthesis</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Molecular Mimicry</topic><topic>Molecular Sequence Data</topic><topic>Parasites</topic><topic>Protein Structure, Tertiary</topic><topic>Protozoan Proteins - genetics</topic><topic>Protozoan Proteins - immunology</topic><topic>Receptors, CCR5 - chemistry</topic><topic>Receptors, CCR5 - deficiency</topic><topic>Receptors, CCR5 - genetics</topic><topic>Receptors, CCR5 - metabolism</topic><topic>Recombinant Proteins - genetics</topic><topic>Recombinant Proteins - immunology</topic><topic>Toxoplasma - immunology</topic><topic>Toxoplasma - pathogenicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>e Sousa, Caetano Reis</creatorcontrib><creatorcontrib>Sher, Alan</creatorcontrib><creatorcontrib>Valenzuela, Jesus G</creatorcontrib><creatorcontrib>Charest, Hugues</creatorcontrib><creatorcontrib>Ribeiro, Jose M</creatorcontrib><creatorcontrib>Hieny, Sara</creatorcontrib><creatorcontrib>Carruthers, Vern B</creatorcontrib><creatorcontrib>Aliberti, Julio</creatorcontrib><creatorcontrib>Andersen, John</creatorcontrib><creatorcontrib>Fairlamb, Alan</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: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</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 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>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</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>ProQuest Biological Science Collection</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>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Nature immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>e Sousa, Caetano Reis</au><au>Sher, Alan</au><au>Valenzuela, Jesus G</au><au>Charest, Hugues</au><au>Ribeiro, Jose M</au><au>Hieny, Sara</au><au>Carruthers, Vern B</au><au>Aliberti, Julio</au><au>Andersen, John</au><au>Fairlamb, Alan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular mimicry of a CCR5 binding-domain in the microbial activation of dendritic cells</atitle><jtitle>Nature immunology</jtitle><stitle>Nat Immunol</stitle><addtitle>Nat Immunol</addtitle><date>2003-05-01</date><risdate>2003</risdate><volume>4</volume><issue>5</issue><spage>485</spage><epage>490</epage><pages>485-490</pages><issn>1529-2908</issn><eissn>1529-2916</eissn><abstract>Toxoplasma gondii
releases factors that potently stimulate production of interleukin-12 (IL-12) from dendritic cells (DCs). Purification of this activity showed that cyclophilin-18 (C-18) was its principal component, and antibodies generated against recombinant C-18 inhibited tachyzoite extract–induced synthesis of IL-12. Recombinant C-18 showed high affinity for and triggered cell signaling through CCR5, a chemokine receptor important in parasite-induced IL-12 production by DCs. These findings suggest that the unusual potency of
T. gondii
in inducing IL-12 from DCs results from its synthesis of a unique chemokine mimic that signals through CCR5. The ability to generate this strong protective response may benefit parasite transmission by preventing the protozoan from overwhelming its intermediate hosts.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>12665855</pmid><doi>10.1038/ni915</doi><tpages>6</tpages></addata></record> |
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| subjects | Amino Acid Sequence Animals Base Sequence Biomedical and Life Sciences Biomedicine Calcium Signaling Chemotaxis Cyclophilins - genetics Cyclophilins - immunology Cyclosporine - pharmacology Dendritic Cells - immunology Dendritic Cells - physiology DNA, Protozoan - genetics Immunology In Vitro Techniques Infectious Diseases Interleukin-12 - biosynthesis Mice Mice, Inbred C57BL Mice, Knockout Molecular Mimicry Molecular Sequence Data Parasites Protein Structure, Tertiary Protozoan Proteins - genetics Protozoan Proteins - immunology Receptors, CCR5 - chemistry Receptors, CCR5 - deficiency Receptors, CCR5 - genetics Receptors, CCR5 - metabolism Recombinant Proteins - genetics Recombinant Proteins - immunology Toxoplasma - immunology Toxoplasma - pathogenicity |
| title | Molecular mimicry of a CCR5 binding-domain in the microbial activation of dendritic cells |
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