Journal Article

TLR11 Activation of Dendritic Cells by a Protozoan Profilin-Like Protein

Andersen, John F, Bannenberg, Gerard L, Hayden, Matthew S, Hieny, Sara, Flavell, Richard A, Serhan, Charles N, Sutterwala, Fayyaz S, Yarovinsky, Felix, Ghosh, Sankar, Zhang, Dekai, Sher, Alan

2005

Overview

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.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Adaptor Proteins, Signal Transducing / Amino Acid Motifs / Amino Acid Sequence / Analysis / Analysis of the immune response. Humoral and cellular immunity / Animals / Antigens, Differentiation - genetics / Antigens, Differentiation - metabolism / bacteria / Biological and medical sciences / Cellular biology / Contractile Proteins - chemistry / Contractile Proteins - immunology / Contractile Proteins - isolation & purification / Contractile Proteins - metabolism / Cytokines / Dendritic cells / Dendritic Cells - immunology / Feedback (Response) / Fractions / Fundamental and applied biological sciences. Psychology / Fundamental immunology / Genes, Protozoan / Immunity, Innate / Immunobiology / Individualized Instruction / Infections / interleukin-12 / Interleukin-12 - biosynthesis / Interleukin-12 - blood / Ligands / Membrane Glycoproteins - metabolism / Mice / Mice, Inbred C57BL / Microfilament Proteins - chemistry / Microfilament Proteins - immunology / Microfilament Proteins - isolation & purification / Microfilament Proteins - metabolism / Microorganisms / Molecular Sequence Data / Molecules / Myeloid Differentiation Factor 88 / NF-kappa B - metabolism / Organs and cells involved in the immune response / Parasite hosts / Parasites / Pathogens / Profilins / Proteins / Protozoa / Protozoan enzymes / Protozoan Proteins - chemistry / Protozoan Proteins - immunology / Protozoan Proteins - isolation & purification / Protozoan Proteins - metabolism / Protozoans / Receptors, Cell Surface - metabolism / Receptors, Immunologic - genetics / Receptors, Immunologic - metabolism / Recombinant Proteins - immunology / Scientific Concepts / Signal Transduction / Toll-Like Receptors / Toxoplasma - genetics / Toxoplasma - immunology / Toxoplasma gondii / Toxoplasmosis, Animal - immunology / Transfection / viruses