Contribution of Fimbria and Filamentous hemagglutinin in Bordetella Adherence and Immune Suppression Public Deposited

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  • March 19, 2019
Creator
  • Scheller, Erich
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
Abstract
  • Pertussis, or whooping cough, is a highly contagious respiratory disease caused by Bordetella pertussis. Recent changes to the vaccine against B. pertussis have led to the re-emergence of this disease. Given the re-emergence of pertussis, it is critical to understand Bordetella pathogenesis. Fimbria and filamentous hemagglutinin (FHA), two proposed bacterial adhesins and components of the current vaccine, have been shown to be important virulence factors required for bacterial colonization of the lower respiratory tract of rats. Bordetella fimbria (Type I pili) are generally considered to function as adhesins despite a lack of supporting experimental evidence. FHA is a large exoprotein that has been shown critical for Bordetella adherence. We developed a novel in vivo adherence assay that confirmed FHA functions as an adhesin and we demonstrated a role for fimbria in adherence to ciliated respiratory epithelium. We further established that fimbria are required for bacterial persistence in the lower respiratory tract of mice and that fimbria contribute to suppression of the immune response. We also observed that wild-type and FHA-deficient bacteria induced cellular infiltrate around the major airways of the lungs and that FIM-deficient bacteria induced cellular infiltrate in the alveoli. A bacterial localization assay established that WT and FHA-deficient bacteria localized to the major airways and that FIM-deficient bacteria localized to the alveoli. Together, these findings suggest that fimbria mediate the first critical step of localizing the bacteria to the ciliated epithelium of the major airways, and that FHA may mediate tight adherence to these cells. We also demonstrated that SCID mice, which contain functional neutrophils and macrophages but lack B and T-cells, are unable to clear FIM-deficient bacteria from the lungs. B and T-cells adoptively transferred in to SCID mice prior to inoculation partially restored clearance of FIM-deficient bacteria from the lungs. Collectively, our data suggest that fimbria and FHA mediate critical adherence steps necessary for Bordetella to colonize and to modulate the immune system and that B and/or T-cells are required to mediate the initial host response to control Bordetella infection.
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  • In Copyright
Advisor
  • Braunstein, Miriam
  • Goldman, William
  • Kawula, Thomas
  • Miller, Virginia
  • Cotter, Peggy
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2015
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  • Chapel Hill, NC
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