Cholesterol-rich domains are involved in Bordetella pertussis phagocytosis and intracellular survival in neutrophils.
Bordetella pertussis-specific antibodies protect against whooping cough by facilitating host defense mechanisms such as phagocytosis. However, the mechanism involved in the phagocytosis of the bacteria under non-opsonic conditions is still poorly characterized. We report here that B. pertussis binding and internalization is cholesterol dependent. Furthermore, we found cholesterol to be implicated in B. pertussis survival upon interaction with human neutrophils. Pre-treatment of PMN with cholesterol sequestering drugs like nystatin or methyl-beta-cyclodextrin (MbetaCD) resulted in a drastic decrease of uptake of non-opsonized B. pertussis. Conversely, phagocytosis of opsonized bacteria was not affected by these drugs, showing that cholesterol depletion affects neither the viability of PMN nor the route of entry of opsonized B. pertussis. Additionally, intracellular survival rate of non-opsonized bacteria was significantly decreased in cholesterol-depleted PMN. Accordingly, confocal laser microscopy studies showed that non-opsonized B. pertussis co-localized with lysosomal markers only in cholesterol-depleted PMN but not in normal PMN. Our results indicate that B. pertussis docks to molecules that eventually prevent cellular bactericidal activity.
Lamberti
Yanina
Y
CINDEFI, CONICET, School of Science, La Plata University, La Plata, Argentina.
Perez Vidakovics
Maria Laura
ML
van der Pol
Ludo-W
LW
Rodríguez
Maria Eugenia
ME
D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D001422:Bacterial Adhesion / Q000187:drug effects; D001885:Bordetella Infections / Q000276:immunology / Q000382:microbiology*; D001886:Bordetella pertussis / Q000276:immunology / Q000502:physiology*; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D050296:Microbial Viability; D009504:Neutrophils / Q000737:chemistry* / Q000276:immunology / Q000382:microbiology* / Q000502:physiology; D009761:Nystatin / Q000494:pharmacology; D009895:Opsonin Proteins / Q000097:blood / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects; D017434:Protein Structure, Tertiary; D047392:beta-Cyclodextrins / Q000494:pharmacology
D000907:Antibodies, Bacterial; D009895:Opsonin Proteins; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D009761:Nystatin; D002784:Cholesterol