Cooperation of TLR12 and TLR11 in the IRF8-dependent IL-12 response to Toxoplasma gondii profilin
TLRs play a central role in the innate recognition of pathogens and the activation of dendritic cells (DCs). In this study, we establish that, in addition to TLR11, TLR12 recognizes the profilin protein of the protozoan parasite Toxoplasma gondii and regulates IL-12 production by DCs in response to...
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| Veröffentlicht in: | The Journal of immunology (1950) 2013-11, Vol.191 (9), p.4818-4827 |
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| container_title | The Journal of immunology (1950) |
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| creator | Raetz, Megan Kibardin, Alexey Sturge, Carolyn R Pifer, Reed Li, Haiying Burstein, Ezra Ozato, Keiko Larin, Sergey Yarovinsky, Felix |
| description | TLRs play a central role in the innate recognition of pathogens and the activation of dendritic cells (DCs). In this study, we establish that, in addition to TLR11, TLR12 recognizes the profilin protein of the protozoan parasite Toxoplasma gondii and regulates IL-12 production by DCs in response to the parasite. Similar to TLR11, TLR12 is an endolysosomal innate immune receptor that colocalizes and interacts with UNC93B1. Biochemical experiments revealed that TLR11 and TLR12 directly bind to T. gondii profilin and are capable of forming a heterodimer complex. We also establish that the transcription factor IFN regulatory factor 8, not NF-κB, plays a central role in the regulation of the TLR11- and TLR12-dependent IL-12 response of DCs. These results suggest a central role for IFN regulatory factor 8-expressing CD8(+) DCs in governing the TLR11- and TLR12-mediated host defense against T. gondii. |
| doi_str_mv | 10.4049/jimmunol.1301301 |
| format | Article |
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In this study, we establish that, in addition to TLR11, TLR12 recognizes the profilin protein of the protozoan parasite Toxoplasma gondii and regulates IL-12 production by DCs in response to the parasite. Similar to TLR11, TLR12 is an endolysosomal innate immune receptor that colocalizes and interacts with UNC93B1. Biochemical experiments revealed that TLR11 and TLR12 directly bind to T. gondii profilin and are capable of forming a heterodimer complex. We also establish that the transcription factor IFN regulatory factor 8, not NF-κB, plays a central role in the regulation of the TLR11- and TLR12-dependent IL-12 response of DCs. These results suggest a central role for IFN regulatory factor 8-expressing CD8(+) DCs in governing the TLR11- and TLR12-mediated host defense against T. gondii.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.1301301</identifier><identifier>PMID: 24078692</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Antigens, Protozoan - immunology ; CD8 Antigens - metabolism ; Cell Line ; Dendritic Cells - immunology ; HEK293 Cells ; Humans ; Interferon Regulatory Factors - metabolism ; Interleukin-12 - biosynthesis ; Interleukin-12 - metabolism ; Membrane Transport Proteins - metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myeloid Differentiation Factor 88 - genetics ; NF-kappa B - metabolism ; Profilins - immunology ; Profilins - metabolism ; Protein Binding - immunology ; RNA Interference ; RNA, Small Interfering ; Signal Transduction - immunology ; Toll-Like Receptors - genetics ; Toll-Like Receptors - metabolism ; Toxoplasma - immunology ; Toxoplasma - metabolism ; Toxoplasma gondii ; Toxoplasmosis, Animal - immunology ; Toxoplasmosis, Animal - metabolism ; Toxoplasmosis, Animal - parasitology</subject><ispartof>The Journal of immunology (1950), 2013-11, Vol.191 (9), p.4818-4827</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c495t-361dc3261dae2ba787cf03ca3b9f4ac08b35716dbacee73ad6f631dd3221a14d3</citedby><cites>FETCH-LOGICAL-c495t-361dc3261dae2ba787cf03ca3b9f4ac08b35716dbacee73ad6f631dd3221a14d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24078692$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Raetz, Megan</creatorcontrib><creatorcontrib>Kibardin, Alexey</creatorcontrib><creatorcontrib>Sturge, Carolyn R</creatorcontrib><creatorcontrib>Pifer, Reed</creatorcontrib><creatorcontrib>Li, Haiying</creatorcontrib><creatorcontrib>Burstein, Ezra</creatorcontrib><creatorcontrib>Ozato, Keiko</creatorcontrib><creatorcontrib>Larin, Sergey</creatorcontrib><creatorcontrib>Yarovinsky, Felix</creatorcontrib><title>Cooperation of TLR12 and TLR11 in the IRF8-dependent IL-12 response to Toxoplasma gondii profilin</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>TLRs play a central role in the innate recognition of pathogens and the activation of dendritic cells (DCs). In this study, we establish that, in addition to TLR11, TLR12 recognizes the profilin protein of the protozoan parasite Toxoplasma gondii and regulates IL-12 production by DCs in response to the parasite. Similar to TLR11, TLR12 is an endolysosomal innate immune receptor that colocalizes and interacts with UNC93B1. Biochemical experiments revealed that TLR11 and TLR12 directly bind to T. gondii profilin and are capable of forming a heterodimer complex. We also establish that the transcription factor IFN regulatory factor 8, not NF-κB, plays a central role in the regulation of the TLR11- and TLR12-dependent IL-12 response of DCs. These results suggest a central role for IFN regulatory factor 8-expressing CD8(+) DCs in governing the TLR11- and TLR12-mediated host defense against T. gondii.</description><subject>Animals</subject><subject>Antigens, Protozoan - immunology</subject><subject>CD8 Antigens - metabolism</subject><subject>Cell Line</subject><subject>Dendritic Cells - immunology</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Interferon Regulatory Factors - metabolism</subject><subject>Interleukin-12 - biosynthesis</subject><subject>Interleukin-12 - metabolism</subject><subject>Membrane Transport Proteins - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Myeloid Differentiation Factor 88 - genetics</subject><subject>NF-kappa B - metabolism</subject><subject>Profilins - immunology</subject><subject>Profilins - metabolism</subject><subject>Protein Binding - immunology</subject><subject>RNA Interference</subject><subject>RNA, Small Interfering</subject><subject>Signal Transduction - immunology</subject><subject>Toll-Like Receptors - genetics</subject><subject>Toll-Like Receptors - metabolism</subject><subject>Toxoplasma - immunology</subject><subject>Toxoplasma - metabolism</subject><subject>Toxoplasma gondii</subject><subject>Toxoplasmosis, Animal - immunology</subject><subject>Toxoplasmosis, Animal - metabolism</subject><subject>Toxoplasmosis, Animal - parasitology</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUU1LJDEQDbLLOurePUmOe2mtfHS6-yIsw7oODAgynkN1ktZId9ImPYv777dnHUVPQlFVUK8er-oRcsrgXIJsLh79MGxD7M-ZgF0ckAUrSyiUAvWFLAA4L1ilqkNylPMjACjg8hs55BKqWjV8QXAZ4-gSTj4GGju6Wd8yTjHY_x2jPtDpwdHV7VVdWDe6YF2Y6GpdzKjk8hhDdnSKdBOf49hjHpDex2C9p2OKne99OCFfO-yz-76vx-Tu6tdmeV2sb36vlj_XhZFNORVCMWsEnzM63mJVV6YDYVC0TSfRQN2KsmLKtmicqwRa1SnBrBWcM2TSimNy-cI7btvBWTPrTNjrMfkB018d0euPk-Af9H38o0UNparlTPBjT5Di09blSQ8-G9f3GFzcZj1_lile1aL5HCqlhN331QyFF6hJMefkujdFDPTORP1qot6bOK-cvb_kbeHVNfEPD5eZ3A</recordid><startdate>20131101</startdate><enddate>20131101</enddate><creator>Raetz, Megan</creator><creator>Kibardin, Alexey</creator><creator>Sturge, Carolyn R</creator><creator>Pifer, Reed</creator><creator>Li, Haiying</creator><creator>Burstein, Ezra</creator><creator>Ozato, Keiko</creator><creator>Larin, Sergey</creator><creator>Yarovinsky, Felix</creator><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>7T5</scope><scope>H94</scope><scope>M7N</scope><scope>5PM</scope></search><sort><creationdate>20131101</creationdate><title>Cooperation of TLR12 and TLR11 in the IRF8-dependent IL-12 response to Toxoplasma gondii profilin</title><author>Raetz, Megan ; Kibardin, Alexey ; Sturge, Carolyn R ; Pifer, Reed ; Li, Haiying ; Burstein, Ezra ; Ozato, Keiko ; Larin, Sergey ; Yarovinsky, Felix</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c495t-361dc3261dae2ba787cf03ca3b9f4ac08b35716dbacee73ad6f631dd3221a14d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Antigens, Protozoan - immunology</topic><topic>CD8 Antigens - metabolism</topic><topic>Cell Line</topic><topic>Dendritic Cells - immunology</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Interferon Regulatory Factors - metabolism</topic><topic>Interleukin-12 - biosynthesis</topic><topic>Interleukin-12 - metabolism</topic><topic>Membrane Transport Proteins - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Myeloid Differentiation Factor 88 - genetics</topic><topic>NF-kappa B - metabolism</topic><topic>Profilins - immunology</topic><topic>Profilins - metabolism</topic><topic>Protein Binding - immunology</topic><topic>RNA Interference</topic><topic>RNA, Small Interfering</topic><topic>Signal Transduction - immunology</topic><topic>Toll-Like Receptors - genetics</topic><topic>Toll-Like Receptors - metabolism</topic><topic>Toxoplasma - immunology</topic><topic>Toxoplasma - metabolism</topic><topic>Toxoplasma gondii</topic><topic>Toxoplasmosis, Animal - immunology</topic><topic>Toxoplasmosis, Animal - metabolism</topic><topic>Toxoplasmosis, Animal - parasitology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Raetz, Megan</creatorcontrib><creatorcontrib>Kibardin, Alexey</creatorcontrib><creatorcontrib>Sturge, Carolyn R</creatorcontrib><creatorcontrib>Pifer, Reed</creatorcontrib><creatorcontrib>Li, Haiying</creatorcontrib><creatorcontrib>Burstein, Ezra</creatorcontrib><creatorcontrib>Ozato, Keiko</creatorcontrib><creatorcontrib>Larin, Sergey</creatorcontrib><creatorcontrib>Yarovinsky, Felix</creatorcontrib><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>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Raetz, Megan</au><au>Kibardin, Alexey</au><au>Sturge, Carolyn R</au><au>Pifer, Reed</au><au>Li, Haiying</au><au>Burstein, Ezra</au><au>Ozato, Keiko</au><au>Larin, Sergey</au><au>Yarovinsky, Felix</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cooperation of TLR12 and TLR11 in the IRF8-dependent IL-12 response to Toxoplasma gondii profilin</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2013-11-01</date><risdate>2013</risdate><volume>191</volume><issue>9</issue><spage>4818</spage><epage>4827</epage><pages>4818-4827</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>TLRs play a central role in the innate recognition of pathogens and the activation of dendritic cells (DCs). In this study, we establish that, in addition to TLR11, TLR12 recognizes the profilin protein of the protozoan parasite Toxoplasma gondii and regulates IL-12 production by DCs in response to the parasite. Similar to TLR11, TLR12 is an endolysosomal innate immune receptor that colocalizes and interacts with UNC93B1. Biochemical experiments revealed that TLR11 and TLR12 directly bind to T. gondii profilin and are capable of forming a heterodimer complex. We also establish that the transcription factor IFN regulatory factor 8, not NF-κB, plays a central role in the regulation of the TLR11- and TLR12-dependent IL-12 response of DCs. These results suggest a central role for IFN regulatory factor 8-expressing CD8(+) DCs in governing the TLR11- and TLR12-mediated host defense against T. gondii.</abstract><cop>United States</cop><pmid>24078692</pmid><doi>10.4049/jimmunol.1301301</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Animals Antigens, Protozoan - immunology CD8 Antigens - metabolism Cell Line Dendritic Cells - immunology HEK293 Cells Humans Interferon Regulatory Factors - metabolism Interleukin-12 - biosynthesis Interleukin-12 - metabolism Membrane Transport Proteins - metabolism Mice Mice, Inbred C57BL Mice, Knockout Myeloid Differentiation Factor 88 - genetics NF-kappa B - metabolism Profilins - immunology Profilins - metabolism Protein Binding - immunology RNA Interference RNA, Small Interfering Signal Transduction - immunology Toll-Like Receptors - genetics Toll-Like Receptors - metabolism Toxoplasma - immunology Toxoplasma - metabolism Toxoplasma gondii Toxoplasmosis, Animal - immunology Toxoplasmosis, Animal - metabolism Toxoplasmosis, Animal - parasitology |
| title | Cooperation of TLR12 and TLR11 in the IRF8-dependent IL-12 response to Toxoplasma gondii profilin |
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