title: Complement processing and immunoglobulin binding to Neisseria gonorrhoeae determined in vitro simulates in vivo effects.
abstract: Local inflammation elicited by Neisseria gonorrhoeae correlates closely with sensitivity to killing by normal human serum. Serum-sensitive (SS) isolates are rendered resistant in vitro by lipooligosaccharide sialylation. Differences in C3b processing on N. gonorrhoeae in vitro were found to match findings at the cervical level in vivo. Nonsialylated SS gonococci bound 5-fold more C3b than did stably serum-resistant (SR) gonococci; most was processed to iC3b, yet significant C3b persisted. Sialylated SS gonococci bound 4-fold less total C3 antigen than did SR gonococci, which was promptly converted to iC3b. C3b bound later on stably SR gonococci but again was processed swiftly to iC3b. In vivo, the iC3b/C3 ratio of SS isolates more closely resembled nonsialylated SS isolates in vitro, implying heterogeneous sialylation or desialylation in vivo. In vitro, total IgM bound was unchanged by sialylation of SS isolates, but total C4 bound decreased by 75%, suggesting that sialylation may indirectly regulate the classical complement pathway.
authors.affiliation: Maxwell Finland Laboratory for Infectious Diseases, Boston Medical Center, 774 Albany Street, Boston, Massachusetts, USA. dmcquill@bu.edu
authors.forename: D P
authors.initials: DP
authors.lastname: McQuillen
authors.forename: S
authors.initials: S
authors.lastname: Gulati
authors.forename: S
authors.initials: S
authors.lastname: Ram
authors.forename: A K
authors.initials: AK
authors.lastname: Turner
authors.forename: D B
authors.initials: DB
authors.lastname: Jani
authors.forename: T C
authors.initials: TC
authors.lastname: Heeren
authors.forename: P A
authors.initials: PA
authors.lastname: Rice
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001770:Blood Bactericidal Activity / Q000276:immunology; D003179:Complement C3b / Q000378:metabolism; D011415:Complement Factor B / Q000378:metabolism; D003170:Complement Pathway, Alternative; D003171:Complement Pathway, Classical; D003165:Complement System Proteins / Q000378:metabolism*; D005260:Female; D006069:Gonorrhea / Q000209:etiology / Q000276:immunology / Q000382:microbiology; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology; D051379:Mice; D009344:Neisseria gonorrhoeae / Q000276:immunology* / Q000302:isolation & purification / Q000472:pathogenicity; D012794:Sialic Acids / Q000737:chemistry
chemical_list: D000911:Antibodies, Monoclonal; D007136:Immunoglobulins; D008070:Lipopolysaccharides; D012794:Sialic Acids; D003179:Complement C3b; D003165:Complement System Proteins; D011415:Complement Factor B