title: Induction of proinflammatory cytokines in human lung epithelial cells during Rhodococcus equi infection.
abstract: Rhodococcus equi is an opportunistic human pathogen associated with immunosuppressed people. While the interaction of R. equi with macrophages has been comprehensively studied, little is known about its interactions with non-phagocytic cells. Here, we characterized the entry process of this bacterium into human lung epithelial cells. The invasion is inhibited by nocodazole and wortmannin, suggesting that the phosphatidylinositol 3-kinase pathway and microtubule cytoskeleton are important for invasion. Pre-incubation of R. equi with a rabbit anti-R. equi polyclonal antiserum resulted in a dramatic reduction in invasion. Also, the invasion process as studied by immunofluorescence and scanning electron microscopy indicates that R. equi make initial contact with the microvilli of the A549 cells, and at the structural level, the entry process was observed to occur via a zipper-like mechanism. Infected lung epithelial cells upregulate the expression of cytokines IL-8 and IL-6 upon infection. The production of these pro-inflammatory cytokines was significantly enhanced in culture supernatants from cells infected with non-mucoid plasmid-less strains when compared with cells infected with mucoid strains. These results demonstrate that human airway epithelial cells produce pro-inflammatory mediators against R. equi isolates.
authors.affiliation: Servicio de Microbiología, Hospital Universitario Marqués de Valdecilla-IFIMAV, Santander, Cantabria, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Remuzgo-Martínez
authors.affiliation: Departamento de Biología Molecular, Universidad de Cantabria, Santander, Cantabria, Spain.|Servicio de Microbiología, Hospital Universitario Marqués de Valdecilla-IFIMAV, Santander, Cantabria, Spain.
authors.forename: Lilian
authors.initials: L
authors.lastname: Pilares-Ortega
authors.affiliation: Servicio de Inmunología, Hospital Universitario Marqués de Valdecilla-IFIMAV, Santander, Cantabria, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: Álvarez-Rodríguez
authors.affiliation: Servicio de Microbiología, Hospital Universitario Marqués de Valdecilla-IFIMAV, Santander, Cantabria, Spain.
authors.forename: Maitane
authors.initials: M
authors.lastname: Aranzamendi-Zaldunbide
authors.affiliation: Instituto Universitario de Sanidad Animal, Universidad de Las Palmas de Gran Canaria, Arucas, Gran Canaria, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Padilla
authors.affiliation: Departamento de Anatomía y Biología Celular, Universidad de Cantabria, Santander, Cantabria, Spain.
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Icardo
authors.affiliation: Servicio de Microbiología, Hospital Universitario Marqués de Valdecilla-IFIMAV, Santander, Cantabria, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Ramos-Vivas
mesh_terms: D000193:Actinomycetales Infections / Q000276:immunology* / Q000382:microbiology; D000371:Agglutination; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001422:Bacterial Adhesion; D018441:Biofilms / Q000254:growth & development; D002460:Cell Line; D016207:Cytokines / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology / Q000648:ultrastructure; D015964:Gene Expression Regulation, Bacterial; D054884:Host-Pathogen Interactions; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D008168:Lung / Q000166:cytology; D008870:Microtubules / Q000187:drug effects; D008871:Microvilli; D015739:Nocodazole / Q000494:pharmacology; D058539:Phosphatidylinositol 3-Kinase / Q000187:drug effects; D011817:Rabbits; D016929:Rhodococcus equi / Q000187:drug effects / Q000472:pathogenicity* / Q000502:physiology / Q000648:ultrastructure; D015854:Up-Regulation; D014774:Virulence; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D016207:Cytokines; D007106:Immune Sera; D058539:Phosphatidylinositol 3-Kinase; D015739:Nocodazole; D000077191:Wortmannin