title: Bordetella pertussis modulates human macrophage defense gene expression.
abstract: Bordetella pertussis, the etiological agent of whooping cough, still causes outbreaks. We recently found evidence that B. pertussis can survive and even replicate inside human macrophages, indicating that this host cell might serve as a niche for persistence. In this work, we examined the interaction of B. pertussis with a human monocyte cell line (THP-1) that differentiates into macrophages in culture in order to investigate the host cell response to the infection and the mechanisms that promote that intracellular survival. To that end, we investigated the expression profile of a selected number of genes involved in cellular bactericidal activity and the inflammatory response during the early and late phases of infection. The bactericidal and inflammatory response of infected macrophages was progressively downregulated, while the number of THP-1 cells heavily loaded with live bacteria increased over time postinfection. Two of the main toxins of B. pertussis, pertussis toxin (Ptx) and adenylate cyclase (CyaA), were found to be involved in manipulating the host cell response. Therefore, failure to express either toxin proved detrimental to the development of intracellular infections by those bacteria. Taken together, these results support the relevance of host defense gene manipulation to the outcome of the interaction between B. pertussis and macrophages.
authors.affiliation: CINDEFI (UNLP CONICET La Plata), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 1900 La Plata, Buenos Aires, Argentina.
authors.forename: Hugo Alberto
authors.initials: HA
authors.lastname: Valdez
authors.affiliation: CINDEFI (UNLP CONICET La Plata), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 1900 La Plata, Buenos Aires, Argentina.
authors.forename: Juan Marcos
authors.initials: JM
authors.lastname: Oviedo
authors.affiliation: CINDEFI (UNLP CONICET La Plata), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 1900 La Plata, Buenos Aires, Argentina.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Gorgojo
authors.affiliation: CINDEFI (UNLP CONICET La Plata), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 1900 La Plata, Buenos Aires, Argentina.
authors.forename: Yanina
authors.initials: Y
authors.lastname: Lamberti
authors.affiliation: CINDEFI (UNLP CONICET La Plata), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 1900 La Plata, Buenos Aires, Argentina mer@quimica.unlp.edu.ar.
authors.forename: Maria Eugenia
authors.initials: ME
authors.lastname: Rodriguez
mesh_terms: D001886:Bordetella pertussis / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D052119:Lysosomal-Associated Membrane Protein 2 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D050296:Microbial Viability / Q000276:immunology; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D010587:Phagocytosis; D037521:Virulence Factors / Q000235:genetics; D014917:Whooping Cough / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D052119:Lysosomal-Associated Membrane Protein 2; D037521:Virulence Factors
keywords: Bordetella pertussis; adenylate cyclase; host cell defense response; intracellular survival; pertussis toxin