title: Impaired pro-inflammatory cytokine production and increased Th2-biasing ability of dendritic cells exposed to Taenia excreted/secreted antigens: A critical role for carbohydrates but not for STAT6 signaling.
abstract: In cysticercosis, a parasitic disease caused by cestodes, the details of early interactions between parasite antigens and innate cells from the host are not well understood. In this study, the role of cestode-conditioned dendritic cells (DCs) in priming Th1 versus Th2 responses to bystander antigen was examined by using CD11c(+) DCs as antigen-presenting cells and naive CD4(+) DO11.10 lymphocytes specific to ovalbumin (OVA) as responding cells. No conventional maturation was induced in DCs exposed to Taenia crassiceps excreted/secreted antigens (TcES). The ability of TcES to affect Toll-like receptor (TLR)-mediated maturation and the pro-inflammatory response was analyzed by co-pulsing DCs with TcES and TLR ligands. DCs exposed to TcES blocked TLR4, TLR9 and Toxoplasma soluble antigen-induced phenotypic maturation. TcES-exposed DCs also blocked secretion of pro-inflammatory cytokines and alloreactive T cell proliferation, while preserving IL-10 production. DCs pulsed with TcES+OVA suppressed IFN-gamma, whereas they induced greater IL-4 production by CD4(+) DO11.10 cells. TcES with chemically-altered glycans failed to modulate TLR-mediated activation of DCs and their Th1-inhibitng ability, which was STAT6-independent. Our results reflect the capacity of TcES glyco-antigens to modulate Th1-type and inflammatory responses mediated through DC activation.
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Mexico. literrazas@campus.iztacala.unam.mx
authors.forename: César A
authors.initials: CA
authors.lastname: Terrazas
authors.forename: Lorena
authors.initials: L
authors.lastname: Gómez-García
authors.forename: Luis I
authors.initials: LI
authors.lastname: Terrazas
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000737:chemistry / Q000276:immunology*; D002241:Carbohydrates / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D050800:STAT6 Transcription Factor / Q000276:immunology*; D015398:Signal Transduction; D013621:Taenia / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors; D051217:Toll-Like Receptor 9 / Q000037:antagonists & inhibitors
chemical_list: D000947:Antigens, Helminth; D002241:Carbohydrates; D016207:Cytokines; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9