Modulatory actions of Echinococcus granulosus antigen B on macrophage inflammatory activation
Por:
Folle, AM, Magallanes, SL, Fló, M, Alvez-Rosado, R, Carrión, F, Vallejo, C, Watson, D, Julve, J, González-Sapienza, G, Pristch, O, González-Techera, A, Ferreira, AM
Publicada:
18 mar 2024
Resumen:
Cestodes use own lipid-binding proteins to capture and transport hydrophobic ligands, including lipids that they cannot synthesise as fatty acids and cholesterol. In E. granulosus s.l., one of these lipoproteins is antigen B (EgAgB), codified by a multigenic and polymorphic family that gives rise to five gene products (EgAgB8/1-5 subunits) assembled as a 230 kDa macromolecule. EgAgB has a diagnostic value for cystic echinococcosis, but its putative role in the immunobiology of this infection is still poorly understood. Accumulating research suggests that EgAgB has immunomodulatory properties, but previous studies employed denatured antigen preparations that might exert different effects than the native form, thereby limiting data interpretation. This work analysed the modulatory actions on macrophages of native EgAgB (nEgAgB) and the recombinant form of EgAg8/1, which is the most abundant subunit in the larva and was expressed in insect S2 cells (rEgAgB8/1). Both EgAgB preparations were purified to homogeneity by immunoaffinity chromatography using a novel nanobody anti-EgAgB8/1. nEgAgB and rEgAgB8/1 exhibited differences in size and lipid composition. The rEgAgB8/1 generates mildly larger lipoproteins with a less diverse lipid composition than nEgAgB. Assays using human and murine macrophages showed that both nEgAgB and rEgAgB8/1 interfered with in vitro LPS-driven macrophage activation, decreasing cytokine (IL-1 beta, IL-6, IL-12p40, IFN-beta) secretion and center dot NO generation. Furthermore, nEgAgB and rEgAgB8/1 modulated in vivo LPS-induced cytokine production (IL-6, IL-10) and activation of large (measured as MHC-II level) and small (measured as CD86 and CD40 levels) macrophages in the peritoneum, although rEgAgB8/1 effects were less robust. Overall, this work reinforced the notion that EgAgB is an immunomodulatory component of E. granulosus s.l. Although nEgAgB lipid's effects cannot be ruled out, our data suggest that the EgAgB8/1 subunit contributes to EgAgB ' s ability to regulate the inflammatory activation of macrophages.
Filiaciones:
Folle, AM:
Univ Republica, Fac Ciencias, Unidad Inmunol, Inst Quim Biol, Montevideo, Uruguay
Univ Republica, Fac Quim, Dept Biociencias, Area Inmunol, Montevideo, Montevideo, Uruguay
Magallanes, SL:
Univ Republica, Fac Ciencias, Unidad Inmunol, Inst Quim Biol, Montevideo, Uruguay
Univ Republica, Fac Quim, Dept Biociencias, Area Inmunol, Montevideo, Montevideo, Uruguay
Fló, M:
Inst Pasteur, Unidad Biofis Prot, Montevideo, Uruguay
Alvez-Rosado, R:
Univ Republica, Fac Ciencias, Unidad Inmunol, Inst Quim Biol, Montevideo, Uruguay
Univ Republica, Fac Quim, Dept Biociencias, Area Inmunol, Montevideo, Montevideo, Uruguay
Carrión, F:
Inst Pasteur, Unidad Biofis Prot, Montevideo, Uruguay
Vallejo, C:
Univ Republica, Fac Ciencias, Unidad Inmunol, Inst Quim Biol, Montevideo, Uruguay
Univ Republica, Fac Quim, Dept Biociencias, Area Inmunol, Montevideo, Montevideo, Uruguay
Watson, D:
Univ Strathclyde, Inst Pharm & Biomed Sci, Glasgow, Scotland
Julve, J:
Inst Recerca ST PAU, Res Grp Endocrinol Diabet & Nutr, Barcelona, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Diabet & Enfermedades Metab, Madrid, Spain
González-Sapienza, G:
Univ Republica, Fac Ciencias, Unidad Inmunol, Inst Quim Biol, Montevideo, Uruguay
Univ Republica, Fac Quim, Dept Biociencias, Area Inmunol, Montevideo, Montevideo, Uruguay
Pristch, O:
Inst Pasteur, Unidad Biofis Prot, Montevideo, Uruguay
González-Techera, A:
Univ Republica, Fac Ciencias, Unidad Inmunol, Inst Quim Biol, Montevideo, Uruguay
Univ Republica, Fac Quim, Dept Biociencias, Area Inmunol, Montevideo, Montevideo, Uruguay
Ferreira, AM:
Univ Republica, Fac Ciencias, Unidad Inmunol, Inst Quim Biol, Montevideo, Uruguay
Univ Republica, Fac Quim, Dept Biociencias, Area Inmunol, Montevideo, Montevideo, Uruguay
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