Bordetella adenylate cyclase toxin mobilizes its β2 integrin receptor into lipid rafts to accomplish translocation across target cell membrane in two steps
Abstract
The adenylate cyclase toxin (CyaA) of pathogenic Bordetellae eliminates the first line of host innate immune defense. It penetrates myeloid phagocytes, such as neutrophils, macrophage or dendritic cells, and subverts their signaling by catalyzing an extremely rapid conversion of intracellular ATP to the key signaling molecule cAMP.
This efficiently inhibits the oxidative burst and complement- mediated opsonophagocytic killing of bacteria, thus enabling the pathogen to colonize host airways. We show that translocation of CyaA into phagocyte cytosol occurs in two steps.
The toxin first binds the integrin CD11b/CD18 and inserts into phagocyte membrane to mediate influx of calcium ions into cells. This promotes relocation of the toxin-receptor complex into specific lipid microdomains within cell membrane called rafts.