Interactions Between Endemic Bordetella Species and Host Immunity
Open Access
- Author:
- Wolfe, Daniel N.
- Graduate Program:
- Pathobiology
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- September 28, 2007
- Committee Members:
- Eric Thomas Harvill, Committee Chair/Co-Chair
Avery August, Committee Member
Reka Z Albert, Committee Member
Biao He, Committee Member
Mary J Kennett, Committee Member - Keywords:
- infectious disease
bacteria
parapertussis
Bordetella
whooping cough - Abstract:
- Bordetella pertussis and Bordetella parapertussis are bacterial pathogens that cause whooping cough, a disease that is re-emerging in vaccinated populations. The diseases caused by these bacteria are clinically indistinguishable, but pertussis toxin, which is only expressed by B. pertussis, has a variety of effects on the host immune response and hinders the clearance of B. pertussis from the respiratory tract. This led us to investigate the host factors that overcome the effects of pertussis toxin. In a mouse model of infection, Tumor Necrosis Factor-á was required to limit leukocyte accumulation and survive during infection by B. pertussis, but not a pertussis toxin-deficient strain of B. pertussis. Interferon-ã combatted the effects of pertussis toxin by contributing to the recruitment of leukocytes and the antibody-mediated clearance of B. pertussis. Interestingly, B. parapertussis does not express pertussis toxin but causes the same disease in the same host. We sought to elucidate the host factors that protect against B. parapertussis infection and how this bacterium may evade host immunity. Antibodies, T cells, and neutrophils were crucial to the elimination of B. parapertussis from the respiratory tract. However, B. parapertussis did not stimulate an early Toll-like receptor-4-mediated recruitment of leukocytes to the site of infection, resulting in the evasion of rapid clearance. Interferon-ã overcame the lack of Toll-like receptor-4 stimulation by contributing to the inflammatory response, but Interferon-ã production was inhibited by Interleukin-10, facilitating the persistence of the infection. Ultimately, both B. pertussis and B. parapertussis infections induce protective immunity. Since ecological theory predicts that two closely related immunizing pathogens can not coexist in the same host population, we assessed the cross reactivity of immunity to these pathogens. Immunity induced by B. parapertussis protected against both species while immunity induced by B. pertussis only protected against B. pertussis. O antigen enabled B. parapertussis to avoid cross immunity and may be a key protective antigen. These studies contribute to the understanding of interactions between the bordetellae and host immunity and will guide any future vaccine design against B. parapertussis.