Characterization of murine lung inflammation after infection with parental Bordetella pertussis and mutants deficient in adhesins or toxins.
Bordetella pertussis expresses factors such as filamentous hemagglutinin, agglutinogens, pertactin, and pertussis toxin, which participate in bacterial adhesion; pertussis toxin, dermonecrotic toxin, lipopolysaccharide, and tracheal cytotoxin, which are responsible for toxic effects; and adenylate cyclase-hemolysin, which is required to initiate infection. By using a murine respiratory model, we showed that the RGD sequences of filamentous hemagglutinin and pertactin are important for bacterial persistence. However, mutants deficient in filamentous hemagglutinin and agglutinogens or in pertactin and the RGD sequence of filamentous hemagglutinin behaved as did wild-type B. pertussis, i.e., induced bronchopneumonia, alveolitis, and an influx of macrophages, lymphocytes, and polymorphonuclear leukocytes into bronchoalveolar lavage fluids. These results suggest that these adhesins are not involved in the induction of pulmonary lesions following infection. The intensity of inflammation was markedly reduced after infection with mutants deficient in either hemolytic activity or pertussis toxin expression, whereas a mutant devoid of adenylate cyclase activity behaved as did the avirulent mutant. Pertussis toxin and adenylate cyclase-hemolysin may act indirectly by altering immune cell functions and thus allowing other factors, such as filamentous hemagglutinin, agglutinogens, and pertactin, to trigger adhesion and lipopolysaccharide, dermonecrotic toxin, and tracheal cytotoxin to induce their toxic effects. However, it is possible that pertussis toxin is also responsible for the induction of some pulmonary alterations.
Khelef
N
N
Centre National de Référence des Bordetelles, Unité de Bactériologie Moléculaire et Médicale, Institut Pasteur, Paris, France.
Bachelet
C M
CM
Vargaftig
B B
BB
Guiso
N
N
D000595:Amino Acid Sequence; D000818:Animals; D001422:Bacterial Adhesion / Q000235:genetics*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D001427:Bacterial Toxins / Q000235:genetics; D001886:Bordetella pertussis / Q000235:genetics* / Q000472:pathogenicity*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015815:Cell Adhesion Molecules / Q000235:genetics; D004195:Disease Models, Animal; D006388:Hemagglutinins / Q000235:genetics; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D008168:Lung / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000235:genetics; D011650:Pulmonary Alveoli / Q000382:microbiology / Q000473:pathology; D014774:Virulence / Q000235:genetics; D010566:Virulence Factors, Bordetella; D014917:Whooping Cough / Q000209:etiology / Q000473:pathology*
D001425:Bacterial Outer Membrane Proteins; D001427:Bacterial Toxins; D015815:Cell Adhesion Molecules; D006388:Hemagglutinins; D009842:Oligopeptides; D010566:Virulence Factors, Bordetella; C068929:pertactin; C047981:arginyl-glycyl-aspartic acid