TLR11 activation of dendritic cells by a protozoan profilin-like protein.
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.
Yarovinsky
Felix
F
Immunobiology Section, Laboratory of Parasitic Diseases; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. fyarovinsky@niaid.nih.gov
Zhang
Dekai
D
Andersen
John F
JF
Bannenberg
Gerard L
GL
Serhan
Charles N
CN
Hayden
Matthew S
MS
Hieny
Sara
S
Sutterwala
Fayyaz S
FS
Flavell
Richard A
RA
Ghosh
Sankar
S
Sher
Alan
A
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
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