Critical roles of complement and antibodies in host defense mechanisms against Neisseria meningitidis as revealed by human complement genetic deficiencies.
Certain complement defects are associated with an increased propensity to contract Neisseria meningitidis infections. We performed detailed analyses of complement-mediated defense mechanisms against N. meningitidis 44/76 with whole blood and serum from two adult patients who were completely C2 or C5 deficient. The C5-deficient patient and the matched control were also deficient in mannose-binding lectin (MBL). The proliferation of meningococci incubated in freshly drawn whole blood was estimated by CFU and quantitative DNA real-time PCR. The serum bactericidal activity and opsonophagocytic activity by granulocytes were investigated, including heat-inactivated postvaccination sera, to examine the influence of antimeningococcal antibodies. The meningococci proliferated equally in C2- and C5-deficient blood, with a 2 log(10) increase of CFU and 4- to 5-log(10) increase in DNA copies. Proliferation was modestly decreased in reconstituted C2-deficient and control blood. After reconstitution of C5-deficient blood, all meningococci were killed, which is consistent with high antibody titers being present. The opsonophagocytic activity was strictly C2 dependent, appeared with normal serum, and increased with postvaccination serum. Serum bactericidal activity was strictly dependent on C2, C5, and high antibody titers. MBL did not influence any of the parameters observed. Complement-mediated defense against meningococci was thus dependent on the classical pathway. Some opsonophagocytic activity occurred despite low levels of antimeningococcal antibodies but was more efficient with immune sera. Serum bactericidal activity was dependent on C2, C5, and immune sera. MBL did not influence any of the parameters observed.
Hellerud
Bernt Christian
BC
Rikshospitalet University Hospital, Institute of Immunology, NO-0027 Oslo, Norway. b.c.hellerud@medisin.uio.no
Aase
Audun
A
Herstad
Tove Karin
TK
Naess
Lisbeth Meyer
LM
Kristiansen
Lisa Høyem
LH
Trøseid
Anne-Marie Siebke
AM
Harboe
Morten
M
Lappegård
Knut Tore
KT
Brandtzaeg
Petter
P
Høiby
E Arne
EA
Mollnes
Tom Eirik
TE
D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000097:blood / Q000276:immunology*; D003175:Complement C2 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D003182:Complement C5 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D009345:Neisseria meningitidis / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000906:Antibodies; D003175:Complement C2; D003182:Complement C5