Advisory Committee Chair
David Briles
Advisory Committee Members
Susan Hollingshead
Moon Nahm
Adrie Steyn
Alexander Szalai
Document Type
Dissertation
Date of Award
2007
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
Streptococcus pneumoniae is the most frequently isolated pathogen causing bacteremia in young children and elderly adults. Complement-dependent opsonophagocytosis is thought to be essential to eliminate pneumococci from the circulation. Pneumococci are reported to attach to erythrocytes through immune adherence (IA), a complement and antibody- dependent process that facilitates phagocytosis of pneumococci. In these studies we have determined that protein (chapter 1) and polysaccharide (chapter 2) virulence factors of pneumococci can interfere with this process and that antibody to pneumococci can enhance this process. Using PspA and/or PspC negative strains and complement-deficient mouse sera, we demonstrated that PspA inhibits complement C1q deposition, thus inhibiting C3 activation and deposition via the classical-pathway of complement. In the presence of PspA, PspC had no effect on C3 deposition, but in the absence of PspA we observed much more C3 deposition if PspC was absent than if it was present. PspC's effect appeared to be blocking C3 deposition that was dependent on the alternative pathway. The IA of pneumococci to erythrocytes and the transfer of pneumococci from erythrocytes to macrophages were inhibited by the synergistic effects of PspA and PspC on C3 deposition. The critical role of C3 on IA of pneumococci and the ability of anti-capsule antibody to increase C3 deposition indicate that IA may aid anti-capsule antibody to facilitate iii clearance of pneumococci. Using pneumococcal strain WU2 (capsule type 3) and its nonencapsulated mutant JD908, we demonstrated that an absence of capsule increases complement C3 deposition on JD908, and anti-capsule type 3 monoclonal antibody (mAb) increases complement C3, C1q and C4 deposition on WU2, which enhances the IA of WU2 to erythrocytes. The transfer of WU2 from erythrocytes to macrophages was also enhanced by anti-capsule type 3 mAb. CR3 is required for the transfer reaction of WU2, and FcγRIII/II on macrophages is supplemental. Using pre- and post- vaccination sera of human immunized with the 23-valent pneumococcal polysaccharide vaccine, we demonstrated that human anti-capsule antibodies are also able to increase the IA of pneumococci and their subsequent transfer to macrophages.
Recommended Citation
Li, Jie, "The Role Of Complement In The Clearance Of Streptococcus Pneumoniae Through Immune Adherence" (2007). All ETDs from UAB. 3745.
https://digitalcommons.library.uab.edu/etd-collection/3745