title: Brucella cyclic β-1,2-glucan plays a critical role in the induction of splenomegaly in mice.
abstract: Brucella, the etiological agent of animal and human brucellosis, is a bacterium with the capacity to modulate the inflammatory response. Cyclic β-1,2-glucan (CβG) is a virulence factor key for the pathogenesis of Brucella as it is involved in the intracellular life cycle of the bacteria. Using comparative studies with different CβG mutants of Brucella, cgs (CβG synthase), cgt (CβG transporter) and cgm (CβG modifier), we have identified different roles for this polysaccharide in Brucella. While anionic CβG is required for bacterial growth in low osmolarity conditions, the sole requirement for a successful Brucella interaction with mammalian host is its transport to periplasmic space. Our results uncover a new role for CβG in promoting splenomegaly in mice. We showed that CβG-dependent spleen inflammation is the consequence of massive cell recruitment (monocytes, dendritics cells and neutrophils) due to the induction of pro-inflammatory cytokines such as IL-12 and TNF-α and also that the reduced splenomegaly response observed with the cgs mutant is not the consequence of changes in expression levels of the characterized Brucella PAMPs LPS, flagellin or OMP16/19. Complementation of cgs mutant with purified CβG increased significantly spleen inflammation response suggesting a direct role for this polysaccharide.
authors.affiliation: Instituto de Investigaciones Biotecnológicas "Rodolfo Ugalde" - Instituto Tecnológico de Chascomús (IIB-INTECH), Universidad Nacional de San Martín (UNSAM), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
authors.forename: Mara S
authors.initials: MS
authors.lastname: Roset
authors.affiliation: Laboratorio de Inmunogenética, INIGEM-CONICET, Hospital de Clínicas "José de San Martín," Facultad de Medicina, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina.
authors.forename: Andrés E
authors.initials: AE
authors.lastname: Ibañez
authors.affiliation: Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Job Alves
authors.initials: JA
authors.lastname: de Souza Filho
authors.affiliation: Instituto de Investigaciones Biotecnológicas "Rodolfo Ugalde" - Instituto Tecnológico de Chascomús (IIB-INTECH), Universidad Nacional de San Martín (UNSAM), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Spera
authors.affiliation: Instituto de Investigaciones Biotecnológicas "Rodolfo Ugalde" - Instituto Tecnológico de Chascomús (IIB-INTECH), Universidad Nacional de San Martín (UNSAM), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Minatel
authors.affiliation: Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Sergio C
authors.initials: SC
authors.lastname: Oliveira
authors.affiliation: Laboratorio de Inmunogenética, INIGEM-CONICET, Hospital de Clínicas "José de San Martín," Facultad de Medicina, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina.
authors.forename: Guillermo H
authors.initials: GH
authors.lastname: Giambartolomei
authors.affiliation: Instituto de Investigaciones Biotecnológicas "Rodolfo Ugalde" - Instituto Tecnológico de Chascomús (IIB-INTECH), Universidad Nacional de San Martín (UNSAM), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
authors.forename: Juliana
authors.initials: J
authors.lastname: Cassataro
authors.affiliation: Instituto de Investigaciones Biotecnológicas "Rodolfo Ugalde" - Instituto Tecnológico de Chascomús (IIB-INTECH), Universidad Nacional de San Martín (UNSAM), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Briones
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000818:Animals; D002003:Brucella abortus / Q000235:genetics / Q000378:metabolism; D002006:Brucellosis / Q000382:microbiology*; D016207:Cytokines / Q000378:metabolism; D055786:Gene Knockout Techniques; D005964:Glucosyltransferases / Q000235:genetics; D007249:Inflammation / Q000382:microbiology*; D051379:Mice; D013163:Splenomegaly / Q000382:microbiology*; D047071:beta-Glucans / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; C484700:Cgt protein, Brucella abortus; D016207:Cytokines; D047071:beta-Glucans; C080135:cyclic beta(1-2)glucan; D005964:Glucosyltransferases; C040232:glucan synthase