title: Bordetella parapertussis Circumvents Neutrophil Extracellular Bactericidal Mechanisms.
abstract: B. parapertussis is a whooping cough etiological agent with the ability to evade the immune response induced by pertussis vaccines. We previously demonstrated that in the absence of opsonic antibodies B. parapertussis hampers phagocytosis by neutrophils and macrophages and, when phagocytosed, blocks intracellular killing by interfering with phagolysosomal fusion. But neutrophils can kill and/or immobilize extracellular bacteria through non-phagocytic mechanisms such as degranulation and neutrophil extracellular traps (NETs). In this study we demonstrated that B. parapertussis also has the ability to circumvent these two neutrophil extracellular bactericidal activities. The lack of neutrophil degranulation was found dependent on the O antigen that targets the bacteria to cell lipid rafts, eventually avoiding the fusion of nascent phagosomes with specific and azurophilic granules. IgG opsonization overcame this inhibition of neutrophil degranulation. We further observed that B. parapertussis did not induce NETs release in resting neutrophils and inhibited NETs formation in response to phorbol myristate acetate (PMA) stimulation by a mechanism dependent on adenylate cyclase toxin (CyaA)-mediated inhibition of reactive oxygen species (ROS) generation. Thus, B. parapertussis modulates neutrophil bactericidal activity through two different mechanisms, one related to the lack of proper NETs-inducer stimuli and the other one related to an active inhibitory mechanism. Together with previous results these data suggest that B. parapertussis has the ability to subvert the main neutrophil bactericidal functions, inhibiting efficient clearance in non-immune hosts.
authors.affiliation: CINDEFI (UNLP CONICET La Plata), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina.
authors.forename: Juan
authors.initials: J
authors.lastname: Gorgojo
authors.affiliation: Institute of Biotechnology and Molecular Biology, CCT-La Plata, CONICET-UNLP, La Plata, Argentina.
authors.forename: Emilia
authors.initials: E
authors.lastname: Scharrig
authors.affiliation: Institute of Biotechnology and Molecular Biology, CCT-La Plata, CONICET-UNLP, La Plata, Argentina.
authors.forename: Ricardo M
authors.initials: RM
authors.lastname: Gómez
authors.affiliation: Center for Vaccines and Immunology, Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia Athens, Georgia, United States of America.
authors.forename: Eric T
authors.initials: ET
authors.lastname: Harvill
authors.affiliation: CINDEFI (UNLP CONICET La Plata), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina.
authors.forename: Maria Eugenia
authors.initials: ME
authors.lastname: Rodríguez
mesh_terms: D000907:Antibodies, Bacterial / Q000276:immunology*; D001885:Bordetella Infections / Q000276:immunology* / Q000382:microbiology; D042483:Bordetella parapertussis / Q000254:growth & development* / Q000276:immunology / Q000472:pathogenicity; D065206:Extracellular Traps / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D021962:Membrane Microdomains; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology; D010587:Phagocytosis / Q000276:immunology; D010588:Phagosomes / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial