title: Plasmodium falciparum: differential merozoite dose requirements for maximal production of various inflammatory cytokines.
abstract: The ligand specificity of TLRs and the details of signaling pathways that are activated by ligand-receptor engagements have been studied extensively. However, it is not known whether the signaling events initiated by defined doses of ligand are uniformly effective in producing various cytokines. In this study, we investigated the dose requirement for the saturated production of representative inflammatory cytokines, TNF-α, IL-6 and IL-12, by DCs stimulated with Plasmodium falciparum merozoites/protein-DNA complex or a CpG ODN TLR9 ligand. The data demonstrate that the ligand doses required for the maximal expression of TNF-α and IL-6 are substantially higher than those required for the maximal production of IL-12. The data also demonstrate that the uptake capacity of malaria parasite by plasmacytoid DCs is markedly lower than that of myeloid DCs, and that, like myeloid DCs, plasmacytoid DCs produce significant levels of TNF-α and IL-12 when the uptake of malarial DNA is facilitated by carrier molecules such as polylysine or cationic lipids. These results have implications for enhancing the effectiveness of vaccine against malaria by modulating the innate immune responses of plasmacytoid DCs to malaria parasites.
authors.affiliation: Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey Medical Center, 500 University Drive, Hershey, PA 17033, USA.
authors.forename: Xianzhu
authors.initials: X
authors.lastname: Wu
authors.forename: Nagaraj M
authors.initials: NM
authors.lastname: Gowda
authors.forename: D Channe
authors.initials: DC
authors.lastname: Gowda
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D016054:DNA, Protozoan / Q000302:isolation & purification; D018664:Interleukin-12 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008024:Ligands; D052940:Merozoites / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D013047:Specific Pathogen-Free Organisms; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D016054:DNA, Protozoan; D015850:Interleukin-6; D008024:Ligands; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12