THE ROLE OF PHAGOCYTIC DEFENSES AND INNATE IMMUNITY IN THE CLEARANCE OF BORDETELLA PERTUSSIS INFECTIONS
Bordetella pertussis is the causative agent of the human respiratory disease whooping cough. Despite extensive vaccine coverage, the incidence of this disease continues to rise throughout the developed and developing world. A major contributor to the success of this pathogen, and the focus of this thesis, is its ability to evade and suppress the host innate immune response. The potential of human monocytes to mediate the clearance of B. pertussis infection was examined. Monocytes internalized only a small percentage of the bacteria and pre-treatment with purified pertussis toxin caused a further inhibition in the ability of monocytes to internalize wild-type bacteria. Opsonization with human immune serum played only a modest role in promoting phagocytosis by monocytes. Less than one percent of internalized bacteria remained viable following internalization. Surfactant proteins A (SP-A) and D (SP-D) and play an important role in the innate immune defenses of the respiratory tract. SP-A binds to the lipid A region of lipopolysaccharide (LPS), and SP-D binds to the core oligosaccharide of LPS. Both proteins induce aggregation, promote phagocytosis and killing by neutrophils and macrophages, and have direct antimicrobial activity. B. pertussis LPS has a branched core structure and a non-repeating terminal trisaccharide. Interaction of B. pertussis with these proteins was examined. Wild type B. pertussis, and the related veterinary pathogen B. bronchiseptica, resisted the antimicrobial effects of SP-A and SP-D. However, LPS mutants lacking the terminal trisaccharide of LPS were susceptible to both proteins.
School:University of Cincinnati
School Location:USA - Ohio
Source Type:Master's Thesis
Keywords:bordetella innate immunity sp a d phagocytosis
Date of Publication:01/01/2004