title: TLR11 activation of dendritic cells by a protozoan profilin-like protein.
abstract: Mammalian Toll-like receptors (TLRs) play an important role in the innate recognition of pathogens by dendritic cells (DCs). Although TLRs are clearly involved in the detection of bacteria and viruses, relatively little is known about their function in the innate response to eukaryotic microorganisms. Here we identify a profilin-like molecule from the protozoan parasite Toxoplasma gondii that generates a potent interleukin-12 (IL-12) response in murine DCs that is dependent on myeloid differentiation factor 88. T. gondii profilin activates DCs through TLR11 and is the first chemically defined ligand for this TLR. Moreover, TLR11 is required in vivo for parasite-induced IL-12 production and optimal resistance to infection, thereby establishing a role for the receptor in host recognition of protozoan pathogens.
authors.affiliation: Immunobiology Section, Laboratory of Parasitic Diseases; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. fyarovinsky@niaid.nih.gov
authors.forename: Felix
authors.initials: F
authors.lastname: Yarovinsky
authors.forename: Dekai
authors.initials: D
authors.lastname: Zhang
authors.forename: John F
authors.initials: JF
authors.lastname: Andersen
authors.forename: Gerard L
authors.initials: GL
authors.lastname: Bannenberg
authors.forename: Charles N
authors.initials: CN
authors.lastname: Serhan
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Hayden
authors.forename: Sara
authors.initials: S
authors.lastname: Hieny
authors.forename: Fayyaz S
authors.initials: FS
authors.lastname: Sutterwala
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Sankar
authors.initials: S
authors.lastname: Ghosh
authors.forename: Alan
authors.initials: A
authors.lastname: Sher
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D003285:Contractile Proteins / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D017125:Genes, Protozoan; D007113:Immunity, Innate; D018664:Interleukin-12 / Q000096:biosynthesis / Q000097:blood; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D008969:Molecular Sequence Data; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B / Q000378:metabolism; D051304:Profilins; D015800:Protozoan Proteins / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology; D015398:Signal Transduction; D051193:Toll-Like Receptors; D014122:Toxoplasma / Q000235:genetics / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000276:immunology*; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D003285:Contractile Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C495739:Pfn1 protein, mouse; D051304:Profilins; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; C482903:Tlr11 protein, mouse; D051193:Toll-Like Receptors; D018664:Interleukin-12