title: Antibody-mediated inhibition of Bordetella pertussis adenylate cyclase-haemolysin-induced macrophage cytotoxicity is influenced by variations in the bacterial population.
abstract: Whooping cough is a vaccine-preventable disease presenting with epidemic cycles linked to natural and/or vaccine-driven evolution of the aetiological agent of the disease, Bordetella pertussis. Adenylate cyclase-haemolysin (AC-Hly) is a major toxin produced by this pathogen, which mediates macrophage apoptosis in vitro and in vivo. While current acellular pertussis vaccine (APV) formulations do not include AC-Hly, they all contain pertussis toxin and can comprise filamentous haemagglutinin (FHA), which interacts with AC-Hly, and pertactin (PRN), which has been hypothesized also to interact with AC-Hly. We aimed to study the capacity of specific antibodies to inhibit the in vitro B. pertussis AC-Hly-mediated cytotoxicity of J774A.1 murine macrophages in a background of a changing bacterial population. We demonstrate that: (i) clinical isolates of different types or PRN phenotype are all cytotoxic and lethal in the mouse model of respiratory infection; (ii) lack of PRN production does not impact AC-Hly-related phenotypes; (iii) anti-AC-Hly antibodies inhibit cell lysis whatever the phenotype of the isolate, while anti-PRN antibodies significantly inhibit cell lysis provided the isolate produces this antigen, which might be relevant in vivo for APV-induced immunity; and (iv) anti-FHA antibodies only inhibit lysis induced by isolates collected in 2012, maybe indicating specific characteristics of epidemic lineages of B. pertussis.
authors.affiliation: Institut Pasteur, CNRS-URA3012, Paris, France.|Prevention and Molecular Therapies of Human Diseases Unit, Institut Pasteur, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Hegerle
authors.affiliation: Institut Pasteur, CNRS-URA3012, Paris, France.|Prevention and Molecular Therapies of Human Diseases Unit, Institut Pasteur, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Guiso
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D000907:Antibodies, Bacterial / Q000378:metabolism*; D017209:Apoptosis; D001886:Bordetella pertussis / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival; D004195:Disease Models, Animal; D008264:Macrophages / Q000382:microbiology* / Q000502:physiology*; D051379:Mice; D016019:Survival Analysis; D014917:Whooping Cough / Q000382:microbiology / Q000473:pathology
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D000907:Antibodies, Bacterial