In Vivo Binding of Complement Regulator Factor H by Streptococcus pneumoniae

Quin, Lisa R.; Carmicle, Stephanie; Dave, Sandhya; Pangburn, Michael K.; Evenhuis, Jason P.; McDaniel, Larry S.
December 2005
Journal of Infectious Diseases;12/1/2005, Vol. 192 Issue 11, p1996
Academic Journal
Pneumococcal surface protein C (PspC) binds to the complement regulatory protein factor H (FH), which inhibits alternative pathway activation. In the present study, using a mouse model of systemic infection and flow-cytometric analyses, we demonstrated an in vivo interaction between FH and pneumococci and showed differential FH binding during bacteremia. Flow-cytometric analyses of pneumococci harvested after intra-peritoneal (ip) challenge demonstrated increased binding of PH, compared with that after intravenous (iv) challenge. Real-time polymerase chain reaction analyses of PspC mRNA showed that, relative to pneumococci grown in vitro, those recovered from the blood of mice 24 h after iv challenge exhibited 23-fold higher mRNA levels; however, after ip challenge, PspC mRNA induction was increased 870-fold. A subsequent increase in PspC expression was detected by flow cytometry using a monoclonal antibody against PspC. Furthermore, pneumococci with FH bound to complement before exposure had increased proliferation, compared with pneumococci not pretreated with FH. These results suggest that the interaction between PspC and FH contributes to pneumococcal virulence.


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