title: Nattectin a fish C-type lectin drives Th1 responses in vivo: licenses macrophages to differentiate into cells exhibiting typical DC function.
abstract: Considerable efforts are currently focused on the biology of DC in view of their possible clinical use as adjuvant for the generation of antigen-specific immunity and lifelong immunologic memory or for the treatment of tumors. We assessed the role of Nattectin a C-type lectin identified in the Thalassophryne nattereri fish venom in DC maturation. Nattectin induced a significant neutrophilic recruitment into peritoneal cavity of mice, followed by macrophages, with lipidic mediators and IL-12 p70 synthesis. Macrophages derived from 7day-Nattectin mice were CD11c+CD11b(low)Ly6(high)F4/80R(high) and express high levels of MHC class II and CD80 molecules. Culture of peritoneal exudates derived macrophages from 7day Nattectin-mice and immature BMDCs with Nattectin markedly increased the surface expression of CD40, CD80, CD86, and MHC class II in a dose-dependent manner, and the production of MMP-2 and MMP-9 distributed in nucleus and cytoplasm of cells, that was associated with strong activity in the culture supernatant. Nattectin treated DCs secreted IL-12 p70 and IL-10. The Nattectin-treated BMDC or macrophage-derived DCs were highly efficient at Ag capture. The specific immune response elicited by Nattectin was characterized by the production of specific antibodies IgG1 and mainly IgG2a with IL-10 and IFN-γ synthesis by splenic cells. These results enable us to address that Nattectin induces the recruitment of Ly6C(high) monocytes into the peritoneum, which exhibit a pro-inflammatory profile, where they differentiate into proliferating F4/80R(high) macrophages. Macrophage-derived DCs mature in the presence of the cytokine milieu generated against Nattectin, exhibiting T cell co-stimulatory molecule expression and induced a Th1 polarized response.
authors.affiliation: Immunoregulation Unit, Special Laboratory of Applied Toxinology, CEPID/FAPESP, Butantan Institute, Sao Paulo, Brazil.
authors.forename: Tania Cristina
authors.initials: TC
authors.lastname: Saraiva
authors.forename: Lidiane Zito
authors.initials: LZ
authors.lastname: Grund
authors.forename: Evilin Naname
authors.initials: EN
authors.lastname: Komegae
authors.forename: Anderson Daniel
authors.initials: AD
authors.lastname: Ramos
authors.forename: Katia
authors.initials: K
authors.lastname: Conceição
authors.forename: Noemia M
authors.initials: NM
authors.lastname: Orii
authors.forename: Monica
authors.initials: M
authors.lastname: Lopes-Ferreira
authors.forename: Carla
authors.initials: C
authors.lastname: Lima
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D000943:Antigens, Differentiation / Q000378:metabolism; D024541:Batrachoidiformes / Q000276:immunology; D054338:Cell Transdifferentiation / Q000187:drug effects; D002478:Cells, Cultured; D060833:Cellular Microenvironment / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D029941:Fish Proteins / Q000008:administration & dosage; D007111:Immunity, Cellular / Q000187:drug effects; D037181:Lectins, C-Type / Q000008:administration & dosage*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018417:Th1 Cells / Q000276:immunology; D058408:Th1-Th2 Balance / Q000187:drug effects
chemical_list: D000943:Antigens, Differentiation; D016207:Cytokines; D029941:Fish Proteins; D037181:Lectins, C-Type