Effects of PspA and antibodies to PspA on activation and deposition of complement on the pneumococcal surface.
Streptococcus pneumoniae infection is a frequent cause of pneumonia, otitis media, meningitis, and septicemia. Pneumococcal surface protein A (PspA) is an important virulence factor on the pathogen surface, and it is known to interfere with complement activation. In this study, flow cytometry was used to study the effects of PspA and antibodies to PspA on the deposition of complement C3 on the surface of a capsular type 3 strain, WU2, and its PspA- mutant, JY1119. Using naive mouse serum as a complement source, measurable deposition of C3 was observed within 4 min on PspA- pneumococci, and the amount of surface-bound C3 accumulated rapidly as the amount of serum was increased. In contrast, very little C3 was deposited on the PspA+ strain. In nonimmune mouse serum, the classical pathway was the dominant activation pathway triggered by PspA- pneumococci. Accordingly, EGTA blocked almost all of the complement activation. Moreover, a significant amount of C3 was still deposited on the PspA- strain when serum from factor B-deficient mice was used. This deposition was not observed on the PspA+ pneumococci, indicating that PspA may inhibit complement deposition via the classical pathway. Furthermore, under the conditions we tested, PspA also inhibited C3 deposition when the classical pathway was initiated by antibodies to capsular polysaccharide. Antibodies to PspA could overcome the anticomplementary effect of PspA, allowing for increased complement activation and C3 deposition onto PspA+ bacteria.
Ren
Bing
B
Department of Microbiology, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. bing_ren@microbio.uab.edu
Szalai
Alexander J
AJ
Hollingshead
Susan K
SK
Briles
David E
DE
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D000942:Antigens, Bacterial / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D003167:Complement Activation / Q000187:drug effects; D003176:Complement C3 / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D011008:Pneumococcal Infections / Q000276:immunology / Q000517:prevention & control; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000472:pathogenicity
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D000954:Antigens, Surface; D001426:Bacterial Proteins; D003176:Complement C3; C051592:pneumococcal surface protein A