Bordetella parapertussis Survives the Innate Interaction with Human Neutrophils by Impairing Bactericidal Trafficking inside the Cell through a Lipid Raft-Dependent Mechanism Mediated by the Lipopolysaccharide O Antigen |
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Authors: | Juan Gorgojo Yanina Lamberti Hugo Valdez Eric T Harvill Maria Eugenia Rodríguez |
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Institution: | aCINDEFI (UNLP CONICET La Plata), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina;bDepartment of Veterinary and Biomedical Science, The Pennsylvania State University, University Park, Pennsylvania, USA |
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Abstract: | Whooping cough is a reemerging disease caused by two closely related pathogens, Bordetella pertussis and Bordetella parapertussis. The incidence of B. parapertussis in whooping cough cases has been increasing since the introduction of acellular pertussis vaccines containing purified antigens that are common to both strains. Recently published results demonstrated that these vaccines do not protect against B. parapertussis due to the presence of the O antigen on the bacterial surface that impairs antibody access to shared antigens. We have investigated the effect of the lack of opsonization of B. parapertussis on the outcome of its interaction with human neutrophils (polymorphonuclear leukocytes PMNs]). In the absence of opsonic antibodies, PMN interaction with B. parapertussis resulted in nonbactericidal trafficking upon phagocytosis. A high percentage of nonopsonized B. parapertussis was found in nonacidic lysosome marker (lysosome-associated membrane protein LAMP])-negative phagosomes with access to the host cell-recycling pathway of external nutrients, allowing bacterial survival as determined by intracellular CFU counts. The lipopolysaccharide (LPS) O antigen was found to be involved in directing B. parapertussis to PMN lipid rafts, eventually determining the nonbactericidal fate inside the PMN. IgG opsonization of B. parapertussis drastically changed this interaction by not only inducing efficient PMN phagocytosis but also promoting PMN bacterial killing. These data provide new insights into the immune mechanisms of hosts against B. parapertussis and document the crucial importance of opsonic antibodies in immunity to this pathogen. |
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