title: Echinococcus granulosus Antigen B binds to monocytes and macrophages modulating cell response to inflammation.
abstract: BACKGROUND
  Antigen B (EgAgB) is an abundant lipoprotein released by the larva of the cestode Echinococcus granulosus into the host tissues. Its protein moiety belongs to the cestode-specific family known as hydrophobic ligand binding protein (HLBP), and is encoded by five gene subfamilies (EgAgB8/1-EgAgB8/5). The functions of EgAgB in parasite biology remain unclear. It may play a role in the parasite's lipid metabolism since it carries host lipids that E. granulosus is unable to synthesise. On the other hand, there is evidence supporting immuno-modulating activities in EgAgB, particularly on innate immune cells. Both hypothetical functions might involve EgAgB interactions with monocytes and macrophages, which have not been formally analysed yet.
  
  
  METHODS
  EgAgB binding to monocytes and macrophages was studied by flow cytometry using inflammation-recruited peritoneal cells and the THP-1 cell line. Involvement of the protein and phospholipid moieties in EgAgB binding to cells was analysed employing lipid-free recombinant EgAgB subunits and phospholipase D treated-EgAgB (lacking the polar head of phospholipids). Competition binding assays with plasma lipoproteins and ligands for lipoprotein receptors were performed to gain information about the putative EgAgB receptor(s) in these cells. Arginase-I induction and PMA/LPS-triggered IL-1β, TNF-α and IL-10 secretion were examined to investigate the outcome of EgAgB binding on macrophage response.
  
  
  RESULTS
  Monocytes and macrophages bound native EgAgB specifically; this binding was also found with lipid-free rEgAgB8/1 and rEgAgB8/3, but not rEgAgB8/2 subunits. EgAgB phospholipase D-treatment, but not the competition with phospholipid vesicles, caused a strong inhibition of EgAgB binding activity, suggesting an indirect contribution of phospholipids to EgAgB-cell interaction. Furthermore, competition binding assays indicated that this interaction may involve receptors with affinity for plasma lipoproteins. At functional level, the exposure of macrophages to EgAgB induced a very modest arginase-I response and inhibited PMA/LPS-mediated IL-1β and TNF-α secretion in an IL-10-independent manner.
  
  
  CONCLUSIONS
  EgAgB and, particularly its predominant EgAgB8/1 apolipoprotein, are potential ligands for monocyte and macrophage receptors. These receptors may also be involved in plasma lipoprotein recognition and induce an anti-inflammatory phenotype in macrophages upon recognition of EgAgB.
authors: Cátedra de Inmunología, Facultad de Ciencias/Facultad de Química, Universidad de la República (UdelaR), Montevideo, Uruguay. marivalsil@gmail.com.|Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), Facultad de Ciencias Médicas, Universidad Nacional de La Plata (UNLP), La Plata, Argentina. marivalsil@gmail.com.|Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires, Argentina. marivalsil@gmail.com.
authors: Valeria
authors: V
authors: Silva-Álvarez
authors: Cátedra de Inmunología, Facultad de Ciencias/Facultad de Química, Universidad de la República (UdelaR), Montevideo, Uruguay. maitefolle@gmail.com.
authors: Ana Maite
authors: AM
authors: Folle
authors: Cátedra de Inmunología, Facultad de Ciencias/Facultad de Química, Universidad de la República (UdelaR), Montevideo, Uruguay. analia.ramos@gmail.com.
authors: Ana Lía
authors: AL
authors: Ramos
authors: Laboratório Especial de Toxinologia Aplicada, Center of Toxins, Immune-Response and Cell Signalling (CeTICS), Instituto Butantan, São Paulo, Brazil. eduardosh.kitano@gmail.com.
authors: Eduardo S
authors: ES
authors: Kitano
authors: Laboratório Especial de Toxinologia Aplicada, Center of Toxins, Immune-Response and Cell Signalling (CeTICS), Instituto Butantan, São Paulo, Brazil. leo.iwai@butantan.gov.br.
authors: Leo K
authors: LK
authors: Iwai
authors: Departamento de Bioquímica, Biología Molecular y Genética, Facultad de Veterinaria, Universidad de Extremadura (UNEX), Cáceres, España. corragen@unex.es.
authors: Inés
authors: I
authors: Corraliza
authors: Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), Facultad de Ciencias Médicas, Universidad Nacional de La Plata (UNLP), La Plata, Argentina. bcorsico@gmail.com.|Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires, Argentina. bcorsico@gmail.com.
authors: Betina
authors: B
authors: Córsico
authors: Cátedra de Inmunología, Facultad de Ciencias/Facultad de Química, Universidad de la República (UdelaR), Montevideo, Uruguay. anaferrei25@gmail.com.
authors: Ana María
authors: AM
authors: Ferreira
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D048209:Echinococcus granulosus / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007155:Immunologic Factors / Q000378:metabolism*; D007249:Inflammation / Q000473:pathology*; D008074:Lipoproteins / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011485:Protein Binding
chemical_list: D007155:Immunologic Factors; D008074:Lipoproteins; D010743:Phospholipids; C514022:antigen B, Echinococcus granulosus