An evaluation of the role of properdin in alternative pathway activation on Neisseria meningitidis and Neisseria gonorrhoeae.
Properdin, a positive regulator of the alternative pathway (AP) of complement is important in innate immune defenses against invasive neisserial infections. Recently, commercially available unfractionated properdin was shown to bind to certain biological surfaces, including Neisseria gonorrhoeae, which facilitated C3 deposition. Unfractionated properdin contains aggregates or high-order oligomers, in addition to its physiological "native" (dimeric, trimeric, and tetrameric) forms. We examined the role of properdin in AP activation on diverse strains of Neisseria meningitidis and N. gonorrhoeae specifically using native versus unfractionated properdin. C3 deposition on Neisseria decreased markedly when properdin function was blocked using an anti-properdin mAb or when properdin was depleted from serum. Maximal AP-mediated C3 deposition on Neisseriae even at high (80%) serum concentrations required properdin. Consistent with prior observations, preincubation of bacteria with unfractionated properdin, followed by the addition of properdin-depleted serum resulted in higher C3 deposition than when bacteria were incubated with properdin-depleted serum alone. Unexpectedly, none of 10 Neisserial strains tested bound native properdin. Consistent with its inability to bind to Neisseriae, preincubating bacteria with native properdin followed by the addition of properdin-depleted serum did not cause detectable increases in C3 deposition. However, reconstituting properdin-depleted serum with native properdin a priori enhanced C3 deposition on all strains of Neisseria tested. In conclusion, the physiological forms of properdin do not bind directly to either N. meningitidis or N. gonorrhoeae but play a crucial role in augmenting AP-dependent C3 deposition on the bacteria through the "conventional" mechanism of stabilizing AP C3 convertases.
Agarwal
Sarika
S
Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Ferreira
Viviana P
VP
Cortes
Claudio
C
Pangburn
Michael K
MK
Rice
Peter A
PA
Ram
Sanjay
S
D001422:Bacterial Adhesion / Q000276:immunology; D003176:Complement C3 / Q000378:metabolism; D051561:Complement C3 Convertase, Alternative Pathway / Q000378:metabolism; D003170:Complement Pathway, Alternative / Q000235:genetics / Q000276:immunology*; D004795:Enzyme Stability / Q000276:immunology; D006801:Humans; D009344:Neisseria gonorrhoeae / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D038381:Neisseria meningitidis, Serogroup A / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D038541:Neisseria meningitidis, Serogroup B / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D038542:Neisseria meningitidis, Serogroup C / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D038582:Neisseria meningitidis, Serogroup W-135 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D038581:Neisseria meningitidis, Serogroup Y / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011414:Properdin / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding / Q000276:immunology
D003176:Complement C3; D011414:Properdin; D051561:Complement C3 Convertase, Alternative Pathway