1. Bordetella filamentous hemagglutinin plays a critical role in immunomodulation, suggesting a mechanism for host specificity
- Author
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Inatsuka, Carol S., Julio, Steven M., and Cotter, Peggy A.
- Subjects
Bordetella pertussis -- Research ,Agglutination tests -- Usage ,Science and technology - 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 (FH[A.sub.Bp]) and compared it with wild-type B. bronchiseptica in several naturalhost infection models. FH[A.sub.Bp] was able to substitute for FHA from B. bronchiseptica (FH[A.sub.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 FH[A.sub.Bb] in vivo. Specifically, FH[A.sub.Bb], but not FH[A.sub.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. inflammation | adhesin | respiratory infection | filamentous hemagglutinin
- Published
- 2005