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

GORGOJO, JUAN PABLO; HARVILL, ERIC; RODRIGUEZ, MARÍA EUGENIA

INFECTION AND IMMUNITY

AMER SOC MICROBIOLOGY

Lugar: Washington; Año: 2014 vol. 82 p. 5175 - 5184

0019-9567

Bordetella 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 PMN if specific opsonic antibodies are not present at the site of interaction. We here evaluated the outcome of B. parapertussis innate interaction with human macrophages, a less aggressive type of cells 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. Forty eight hours after infection the wild type B. parapertussis, but not the O antigen deficient mutant, was found colocalizing with lipid rafts and alive in non-acidic 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.