Cholesterol-rich domains are involved in Bordetella pertussis phagocytosis and intracellular survival in neutrophils

• Published in: Microbial pathogenesis 2008-06, Vol.44 (6), p.501-511
• Main Authors: Lamberti, Yanina, Perez Vidakovics, Maria Laura, van der Pol, Ludo-W., Rodríguez, Maria Eugenia
• Format: Article
• Language: English
• Subjects: Antibodies, Bacterial - blood; Antibodies, Bacterial - immunology; Bacterial Adhesion - drug effects; Bacteriology; beta-Cyclodextrins - pharmacology; Biological and medical sciences; Bordetella Infections - immunology; Bordetella Infections - microbiology; Bordetella pertussis; Bordetella pertussis - immunology; Bordetella pertussis - physiology; Cell Membrane - chemistry; Cell Membrane - drug effects; Cell Membrane - metabolism; Cholesterol - chemistry; Cholesterol - metabolism; Fundamental and applied biological sciences. Psychology; Humans; Lipid raft domains; Microbial Viability; Microbiology; Miscellaneous; Neutrophils; Neutrophils - chemistry; Neutrophils - immunology; Neutrophils - microbiology; Neutrophils - physiology; Nystatin - pharmacology; Opsonin Proteins - blood; Opsonin Proteins - immunology; Phagocytosis; Phagocytosis - drug effects; Protein Structure, Tertiary
• ISSN: 0882-4010; 1096-1208
• DOI: 10.1016/j.micpath.2008.01.002

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-β-cyclodextrin (MβCD) 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.