Molecular mimicry of a CCR5 binding-domain in the microbial activation of dendritic cells.
Toxoplasma gondii releases factors that potently stimulate production of interleukin-12 (IL-12) from dendritic cells (DCs). Purification of this activity showed that cyclophilin-18 (C-18) was its principal component, and antibodies generated against recombinant C-18 inhibited tachyzoite extract-induced synthesis of IL-12. Recombinant C-18 showed high affinity for and triggered cell signaling through CCR5, a chemokine receptor important in parasite-induced IL-12 production by DCs. These findings suggest that the unusual potency of T. gondii in inducing IL-12 from DCs results from its synthesis of a unique chemokine mimic that signals through CCR5. The ability to generate this strong protective response may benefit parasite transmission by preventing the protozoan from overwhelming its intermediate hosts.
Aliberti
Julio
J
Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. jaliberti@niaid.nih.gov
Valenzuela
Jesus G
JG
Carruthers
Vern B
VB
Hieny
Sara
S
Andersen
John
J
Charest
Hugues
H
Reis e Sousa
Caetano
C
Fairlamb
Alan
A
Ribeiro
Jose M
JM
Sher
Alan
A
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D020013:Calcium Signaling; D002633:Chemotaxis; D021983:Cyclophilins / Q000235:genetics / Q000276:immunology; D016572:Cyclosporine / Q000494:pharmacology; D016054:DNA, Protozoan / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology* / Q000502:physiology; D066298:In Vitro Techniques; D018664:Interleukin-12 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D019713:Receptors, CCR5 / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D014122:Toxoplasma / Q000276:immunology* / Q000472:pathogenicity
D016054:DNA, Protozoan; D015800:Protozoan Proteins; D019713:Receptors, CCR5; D011994:Recombinant Proteins; D018664:Interleukin-12; D016572:Cyclosporine; D021983:Cyclophilins