BORDETELLA-PERTUSSIS INDUCES APOPTOSIS IN MACROPHAGES - ROLE OF ADENYLATE CYCLASE-HEMOLYSIN

Bordetella pertussis, the causative agent of whooping cough, has been shown recently to enter and survive in epithelial cells and macrophage s in vitro. In the present study, we show that B. pertussis is cytotox ic for J774A.1 cells, a monocyte-macrophage cell line, and for murine alveolar macrophages. We demonstrate that cell cytotoxicity mediated b y B. pertussis occurred through apoptosis, as shown by changes in nucl ear morphology and by host cell DNA fragmentation. Parental strains an d a mutant deficient in pertussis toxin expression are able to induce apoptosis, whereas avirulent mutant or adenylate cyclase-hemolysin-def icient mutants are not cytotoxic. Both adenylate cyclase and hemolytic activities are required for programmed cell death. These results show that induction of apoptosis is dependent on the expression of adenyla te cyclase-hemolysin. The infection of murine alveolar macrophages in primary culture with B. pertussis leads to apoptosis, suggesting that this process might be relevant in vivo. The ability of B. pertussis to promote cell death may be important for the initiation of infection, bacterial survival, and escape of the host immune response.