Cooperation of TLR12 and TLR11 in the IRF8-dependent IL-12 response to Toxoplasma gondii profilin

Megan Raetz, Alexey Kibardin, Carolyn R. Sturge, Reed Pifer, Haiying Li, Ezra Burstein, Keiko Ozato, Sergey Larin, Felix Yarovinsky

Research output: Contribution to journalArticle

49 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)4818-4827
Number of pages10
JournalJournal of Immunology
Volume191
Issue number9
DOIs
StatePublished - Nov 1 2013

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Profilins
Toxoplasma
Interleukin-12
Dendritic Cells
Parasites
Transcription Factors

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Cooperation of TLR12 and TLR11 in the IRF8-dependent IL-12 response to Toxoplasma gondii profilin. / Raetz, Megan; Kibardin, Alexey; Sturge, Carolyn R.; Pifer, Reed; Li, Haiying; Burstein, Ezra; Ozato, Keiko; Larin, Sergey; Yarovinsky, Felix.

In: Journal of Immunology, Vol. 191, No. 9, 01.11.2013, p. 4818-4827.

Research output: Contribution to journalArticle

Raetz, M, Kibardin, A, Sturge, CR, Pifer, R, Li, H, Burstein, E, Ozato, K, Larin, S & Yarovinsky, F 2013, 'Cooperation of TLR12 and TLR11 in the IRF8-dependent IL-12 response to Toxoplasma gondii profilin', Journal of Immunology, vol. 191, no. 9, pp. 4818-4827. https://doi.org/10.4049/jimmunol.1301301
Raetz, Megan ; Kibardin, Alexey ; Sturge, Carolyn R. ; Pifer, Reed ; Li, Haiying ; Burstein, Ezra ; Ozato, Keiko ; Larin, Sergey ; Yarovinsky, Felix. / Cooperation of TLR12 and TLR11 in the IRF8-dependent IL-12 response to Toxoplasma gondii profilin. In: Journal of Immunology. 2013 ; Vol. 191, No. 9. pp. 4818-4827.
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