Toll-like receptor recognition of Toxoplasma gondii.
Toxoplasma gondii potently stimulates IFN-gamma production by both the innate and adaptive immune system as part of its host adaptation. This response is known to be dependent on an Myeloid Differentiation factor 88 signaling pathway used by Toll-like receptors (TLRs), a family of proteins involved in the recognition of microbial molecular patterns. In the following review, we summarise the evidence for specific TLR function in host resistance to T. gondii focusing on the recent discovery in the parasite of a profilin-like ligand that potently stimulates TLR11 and regulates the production of IL-12, a cytokine necessary for the protective IFN-gamma response. In addition, we discuss the hypothesis that TLR11 may have evolved as a general pattern recognition receptor for apicomplexan protozoa and that as highly conserved proteins associated with actin-based motility, profilins are logical ligand targets for this form of pathogen detection. Finally, we review the evidence for involvement of other TLR and TLR ligands in host resistance to T. gondii and discuss how such receptors might synergise with TLR11 in the innate response to the parasite.
Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bld. 50, Rm 6144, 50 South Drive MSC 8003, Bethesda, MD 20892-8003, USA. fyarovinsky@niaid.nih.gov
Felix
F
Yarovinsky
Alan
A
Sher
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D018448:Models, Immunological; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology; D051304:Profilins / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology* / Q000378:metabolism; D014122:Toxoplasma / Q000276:immunology*
D053594:Myeloid Differentiation Factor 88; D051304:Profilins; D051193:Toll-Like Receptors; D018664:Interleukin-12; D007371:Interferon-gamma