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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-\u03baB, 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\u2013expressing CD8+ DCs in governing the TLR11- and TLR12-mediated host defense against T. gondii.<\/jats:p>","DOI":"10.4049\/jimmunol.1301301","type":"journal-article","created":{"date-parts":[[2013,9,28]],"date-time":"2013-09-28T01:03:48Z","timestamp":1380330228000},"page":"4818-4827","source":"Crossref","is-referenced-by-count":125,"title":["Cooperation of TLR12 and TLR11 in the IRF8-Dependent IL-12 Response to\n                    <i>Toxoplasma gondii<\/i>\n                    Profilin"],"prefix":"10.1093","volume":"191","author":[{"given":"Megan","family":"Raetz","sequence":"first","affiliation":[{"name":"Department of Immunology, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey","family":"Kibardin","sequence":"additional","affiliation":[{"name":"Gene Therapy Laboratory, Institute of Gene Biology Russian Academy of Sciences , Moscow 119334,","place":["Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn R","family":"Sturge","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reed","family":"Pifer","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezra","family":"Burstein","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Ozato","sequence":"additional","affiliation":[{"name":"Program in Genomics of Differentiation, National Institute of Child Health and Human Development, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Larin","sequence":"additional","affiliation":[{"name":"Gene Therapy Laboratory, Institute of Gene Biology Russian Academy of Sciences , Moscow 119334,","place":["Russia"]},{"name":"Federal Research Center of Pediatric Hematology, Oncology and Immunology , Moscow 117198,","place":["Russia"]},{"name":"Moscow Institute of Phisics and Technology , Moscow 141700,","place":["Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Yarovinsky","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,11,1]]},"reference":[{"key":"2025032405521962600_r1","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.immuni.2011.05.006","article-title":"Toll-like receptors and their crosstalk with other innate receptors in infection and immunity","volume":"34","author":"Kawai","year":"2011","journal-title":"Immunity"},{"key":"2025032405521962600_r2","doi-asserted-by":"crossref","first-page":"9577","DOI":"10.1073\/pnas.0502272102","article-title":"The evolution of vertebrate Toll-like receptors","volume":"102","author":"Roach","year":"2005","journal-title":"Proc. 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