Killing of Neisseria meningitidis by Human Neutrophils: Implications for Normal and Complement-Deficient Individuals

Abstract

The contributions of complement-dependent phagocytosis and serum bactericidal activity (SBA) to the killing of 62 strains of meningococci were examined by using C8-depleted or pooled human serum (PHS). The complement-dependent nature of killing by neutrophils was confirmed by restoring survival to control values by using heated serum. Serogroups B and 29E, but not A, C, Y, and W135, were ingested and killed by neutrophils in C8-depleted PHS (PHS-C8Dep; 41.7% +/- 7.3% and 60.5% +/- 17.8% vs. greater than or equal to 100% survival, respectively, at 30 min). Group B meningococci were resistant to complement-mediated SBA, whereas group Y were susceptible. Deposition of C3 on serogroups B and Y was similar (28.5 +/- 2.9 vs. 23.5 +/- 2.7 C3 fluorescence units; P greater than .05); however, susceptibility to complement-dependent phagocytosis and complement-mediated SBA of serogroups B and Y did not correlate. We also examined meningococcal phagocytosis by using serum from a C8-deficient patient. In contrast to PHS-C8Dep, this serum supported rapid phagocytic killing of serogroups A, C, Y, and W135 meningococci. This finding suggests that vaccinating individuals deficient in late-complement components may shift the burden of host defense from SBA to phagocytosis.

Binding of the Complement Inhibitor C4bp to Serogroup BNeisseria meningitidis

“…Serogroup B meningococci are more resistant against C-mediated serum bactericidal activity than serogroup Y (30). However, group B strains are susceptible to phagocytosis after opsonization (30). Complement activation results in an increase of the anaphylatoxin C3a and C5a levels, which in concert with activated components of the bradykinin system contribute to endothelial damage, vasodilatation, and capillary leakage.…”

Activity of Human IgG and IgA Subclasses in Immune Defense Against Neisseria meningitidis Serogroup B

“…Serogroup B-specific IgG has been shown to initiate complementmediated lysis of bacteria, as well as leukocyte effector functions such as phagocytosis and respiratory burst (11)(12)(13). Specific IgA has been implicated as a risk factor for disease, because it was shown to impede IgG-mediated bactericidal activity (14), whereas other studies documented its capacity to initiate leukocyte-mediated antimeningococcal activity (15).…”

Background Paper for the update of meningococcal vaccination recommendations in Germany: use of the serogroup B vaccine in persons at increased risk for meningococcal disease

“…In contrast, Plested et al [96,97] showed that serum from a small number of study participants vaccinated with an OMV vaccine with or without an NHBA component and from which C6 was eliminated supported opsonophagocytosis of meningococcal strains with the same PorA as in the OMV components in the presence of polymorphonuclear leukocytes. Finally Ross et al [98] …”