title: Bordetella filamentous hemagglutinin plays a critical role in immunomodulation, suggesting a mechanism for host specificity.
abstract: Bordetella pertussis, the causative agent of the acute childhood respiratory disease whooping cough, is a human-adapted variant of Bordetella bronchiseptica, which displays a broad host range and typically causes chronic, asymptomatic infections. These pathogens express a similar but not identical surface-exposed and secreted protein called filamentous hemagglutinin (FHA) that has been proposed to function as both a primary adhesin and an immunomodulator. To test the hypothesis that FHA plays an important role in determining host specificity and/or the propensity to cause acute versus chronic disease, we constructed a B. bronchiseptica strain expressing FHA from B. pertussis (FHA(Bp)) and compared it with wild-type B. bronchiseptica in several natural-host infection models. FHA(Bp) was able to substitute for FHA from B. bronchiseptica (FHA(Bb)) with regard to its ability to mediate adherence to several epithelial and macrophage-like cell lines in vitro, but it was unable to substitute for FHA(Bb) in vivo. Specifically, FHA(Bb), but not FHA(Bp), allowed B. bronchiseptica to colonize the lower respiratory tracts of rats, to modulate the inflammatory response in the lungs of immunocompetent mice, resulting in decreased lung damage and increased bacterial persistence, to induce a robust anti-Bordetella antibody response in these immunocompetent mice, and to overcome innate immunity and cause a lethal infection in immunodeficient mice. These results indicate a critical role for FHA in B. bronchiseptica-mediated immunomodulation, and they suggest a role for FHA in host specificity.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106-9610, USA.
authors.forename: Carol S
authors.initials: CS
authors.lastname: Inatsuka
authors.forename: Steven M
authors.initials: SM
authors.lastname: Julio
authors.forename: Peggy A
authors.initials: PA
authors.lastname: Cotter
mesh_terms: D018829:Adhesins, Bacterial / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D001884:Bordetella / Q000276:immunology*; D001885:Bordetella Infections / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D016950:Bordetella bronchiseptica / Q000276:immunology; D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D051381:Rats; D013045:Species Specificity; D015996:Survival Rate; D014132:Trachea / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D010566:Virulence Factors, Bordetella / Q000276:immunology* / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; D010566:Virulence Factors, Bordetella; C065273:filamentous hemagglutinin adhesin, Bordetella pertussis