title: Poly-N-Acetylglucosamine Production by Staphylococcus epidermidis Cells Increases Their In Vivo Proinflammatory Effect.
abstract: Poly-N-acetylglucosamine (PNAG) is a major component of the Staphylococcus epidermidis biofilm extracellular matrix. However, it is not yet clear how this polysaccharide impacts the host immune response and infection-associated pathology. Faster neutrophil recruitment and bacterial clearance were observed in mice challenged intraperitoneally with S. epidermidis biofilm cells of the PNAG-producing 9142 strain than in mice similarly challenged with the isogenic PNAG-defective M10 mutant. Moreover, intraperitoneal priming with 9142 cells exacerbated liver inflammatory pathology induced by a subsequent intravenous S. epidermidis challenge, compared to priming with M10 cells. The 9142-primed mice had elevated splenic CD4(+) T cells producing gamma interferon and interleukin-17A, indicating that PNAG promoted cell-mediated immunity. Curiously, despite having more marked liver tissue pathology, 9142-primed mice also had splenic T regulatory cells with greater suppressive activity than those of their M10-primed counterparts. By showing that PNAG production by S. epidermidis biofilm cells exacerbates host inflammatory pathology, these results together suggest that this polysaccharide contributes to the clinical features associated with biofilm-derived infections.
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal ICBAS-UP, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Porto, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Ferreirinha
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
authors.forename: Begoña
authors.initials: B
authors.lastname: Pérez-Cabezas
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Correia
authors.affiliation: Unidade de Pesquisa Clínica do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (UPC-HCFMRP-USP), São Paulo, Brazil.
authors.forename: Bruna
authors.initials: B
authors.lastname: Miyazawa
authors.affiliation: CEB-LIBRO, Centro de Engenharia Biológica, Laboratório de Investigação em Biofilmes Rosário Oliveira, University of Minho, Campus de Gualtar, Braga, Portugal.
authors.forename: Angela
authors.initials: A
authors.lastname: França
authors.affiliation: CEB-LIBRO, Centro de Engenharia Biológica, Laboratório de Investigação em Biofilmes Rosário Oliveira, University of Minho, Campus de Gualtar, Braga, Portugal.
authors.forename: Virgínia
authors.initials: V
authors.lastname: Carvalhais
authors.affiliation: ICBAS-UP, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Porto, Portugal.
authors.forename: Augusto
authors.initials: A
authors.lastname: Faustino
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
authors.forename: Anabela
authors.initials: A
authors.lastname: Cordeiro-da-Silva
authors.affiliation: ICBAS-UP, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Porto, Portugal UMIB, Unidade Multidisciplinar de Investigação Biomédica, Universidade do Porto, Porto, Portugal.
authors.forename: Luzia
authors.initials: L
authors.lastname: Teixeira
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Pier
authors.affiliation: CEB-LIBRO, Centro de Engenharia Biológica, Laboratório de Investigação em Biofilmes Rosário Oliveira, University of Minho, Campus de Gualtar, Braga, Portugal.
authors.forename: Nuno
authors.identifier: 0000-0003-3365-3537
authors.initials: N
authors.lastname: Cerca
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal ICBAS-UP, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Porto, Portugal Vilanova@icbas.up.pt.
authors.forename: Manuel
authors.identifier: 0000-0001-7007-306X
authors.initials: M
authors.lastname: Vilanova
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D018441:Biofilms; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D016207:Cytokines / Q000032:analysis; D004817:Epidermis / Q000378:metabolism*; D005434:Flow Cytometry; D007111:Immunity, Cellular / Q000502:physiology*; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology; D013203:Staphylococcal Infections / Q000503:physiopathology*; D013212:Staphylococcus epidermidis / Q000502:physiology*
chemical_list: D016207:Cytokines; D020381:Interleukin-17; C113831:poly-N-acetyl glucosamine; D007371:Interferon-gamma; D000117:Acetylglucosamine