Bordetella parapertussis Survives inside Human Macrophages in Lipid Raft-Enriched Phagosomes

Abstract

bBordetella parapertussis is a human pathogen that causes whooping cough. The increasing incidence of B. parapertussis has been attributed to the lack of cross protection induced by pertussis vaccines. It was previously shown that B. parapertussis is able to avoid bacterial killing by polymorphonuclear leukocytes (PMN) if specific opsonic antibodies are not present at the site of interaction. Here, we evaluated the outcome of B. parapertussis innate interaction with human macrophages, a less aggressive type of cell and a known reservoir of many persistent pathogens. The results showed that in the absence of opsonins, O antigen allows B. parapertussis to inhibit phagolysosomal fusion and to remain alive inside macrophages. The O antigen targets B. parapertussis to lipid rafts that are retained in the membrane of phagosomes that do not undergo lysosomal maturation. Fortyeight hours after infection, wild-type B. parapertussis bacteria but not the O antigen-deficient mutants were found colocalizing with lipid rafts and alive in nonacidic compartments. Taken together, our data suggest that in the absence of opsonic antibodies, B. parapertussis survives inside macrophages by preventing phagolysosomal maturation in a lipid raft-and O antigen-dependent manner. Two days after infection, about 15% of macrophages were found loaded with live bacteria inside flotillin-enriched phagosomes that had access to nutrients provided by the host cell recycling pathway, suggesting the development of an intracellular infection. IgG opsonization drastically changed this interaction, inducing efficient bacterial killing. These results highlight the need for B. parapertussis opsonic antibodies to induce bacterial clearance and prevent the eventual establishment of cellular reservoirs of this pathogen. Bordetella parapertussis and Bordetella pertussis are human pathogens that cause whooping cough, a reemerging disease that remains a threat to human health. Despite high vaccination coverage, whooping cough is still endemic. Current clinical surveys indicate that B. parapertussis is responsible for a significant number of cases of whooping cough, particularly in vaccinated populations (1-5). The switch from whole-cell to acellular vaccines is associated with a significant increase in the prevalence of B. parapertussis in the epidemiology of the disease (6, 7). Several studies have demonstrated that pertussis acellular vaccines fail to protect against B. parapertussis (6, 8). The lack of cross protection was mainly attributed to the presence of the O antigen on the surface of B. parapertussis, which blocks antibody access to the vaccine antigens common to both species (9, 10). In vitro studies confirmed that pertussis acellular vaccines induce antibodies that opsonize B. pertussis but not B. parapertussis (9, 10). In the absence of opsonic antibodies, B. parapertussis survives neutrophil phagocytosis by preventing lysosomal maturation in a lipid raft-dependent manner (11). O antigen is involved in this nonbactericidal interaction, mediating t...

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Candida albicans Targets a Lipid Raft/Dectin-1 Platform to Enter Human Monocytes and Induce Antigen Specific T Cell Responses

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