title: The Sbi Protein Contributes to Staphylococcus aureus Inflammatory Response during Systemic Infection.
abstract: Staphylococcus aureus is an important human pathogen that causes infections that may present high morbidity and mortality. Among its many virulence factors protein A (SpA) and Staphylococcal binding immunoglobulin protein (Sbi) bind the Fc portion of IgG interfering with opsonophagocytosis. We have previously demonstrated that SpA interacts with the TNF-α receptor (TNFR) 1 through each of the five IgG binding domains and induces the production of pro-inflammatory cytokines and chemokines. The IgG binding domains of Sbi are homologous to those of SpA, which allow us to hypothesize that Sbi might also have a role in the inflammatory response induced by S. aureus. We demonstrate that Sbi is a novel factor that participates in the induction of the inflammatory response during staphylococcal infections via TNFR1 and EGFR mediated signaling as well as downstream MAPKs. The expression of Sbi significantly contributed to IL-6 production and modulated CXCL-1 expression as well as neutrophil recruitment to the site of infection, thus demonstrating for the first time its relevance as a pro-inflammatory staphylococcal antigen in an in vivo model.
authors.affiliation: Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM), Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
authors.forename: Cintia Daniela
authors.initials: CD
authors.lastname: Gonzalez
authors.affiliation: Departamento de Microbiología, Parasitología e Immunología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Camila
authors.initials: C
authors.lastname: Ledo
authors.affiliation: Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM), Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
authors.forename: Constanza
authors.initials: C
authors.lastname: Giai
authors.affiliation: Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM), Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
authors.forename: Ailin
authors.initials: A
authors.lastname: Garófalo
authors.affiliation: Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM), Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina; Departamento de Microbiología, Parasitología e Immunología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Marisa I
authors.initials: MI
authors.lastname: Gómez
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D001666:Binding Sites, Antibody / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology*; D054360:Chemokine CXCL1 / Q000096:biosynthesis; D066246:ErbB Receptors / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007074:Immunoglobulin G / Q000276:immunology; D007249:Inflammation / Q000276:immunology* / Q000382:microbiology; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020556:Neutrophil Infiltration / Q000276:immunology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013203:Staphylococcal Infections / Q000276:immunology*; D013205:Staphylococcal Protein A / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D020032:Tyrphostins / Q000494:pharmacology; D037521:Virulence Factors / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D005419:Flavonoids; D007093:Imidazoles; D007074:Immunoglobulin G; D015850:Interleukin-6; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011799:Quinazolines; D047888:Receptors, Tumor Necrosis Factor, Type I; C112405:Sbi protein, Staphylococcus aureus; D013205:Staphylococcal Protein A; D020032:Tyrphostins; D037521:Virulence Factors; C101044:RTKI cpd; C541485:EGFR protein, mouse; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one