The Role of C3 in Mediating Binding and Ingestion of Group B Streptococcus Serotype III by Murine Macrophages

Abstract

ABSTRACT. To understand how complement effects phagocytosis of type I11 group B streptococcus, we assessed the specific role of C3 in mediating binding and ingestion of these bacteria by macrophages. Phagocytosis of bacteria by resident mouse peritoneal macrophages was measured under conditions in which C3 deposition on bacteria was inhibited or after blockade of C3-ligands or of complement receptor type three (CR3) with specific antibodies. C3 depletion, incubation with F(abf)2 fragments of antibody to C3, or blockade of CR3 completely inhibited the binding of bacteria that was seen in the presence of nonimmune serum. Immune serum increased the number of associated organisms 6-fold compared to that seen with nonimmune serum. With this serum, 82% of organisms were ingested. C3 depletion or CR3 blockage had a modest effect, but this interaction could be ablated completely only after Fc receptors were blocked. Using varied concentrations of an IgG2a MAb against type I11 capsular antigen, it was possible to show that small amounts of antibody incapable of mediating bacterial binding by itself directed an interaction that also depended upon C3. Phagocytosis of group B streptococci by macrophages in the presence of little or no antibody requires complement and C3 opsonization specifically. C3-dependent binding may be important in determining mononuclear phagocyte-dependent clearance of these pathogens from blood, particularly in patients with little or no type-specific serum antibody. (Pediatr Res 30: 118-123,1991) Abbreviations

Survival of Group BStreptococcusType III in Mononuclear Phagocytes: Differential Regulation of Bacterial Killing in Cord Macrophages by Human Recombinant Gamma Interferon and Granulocyte-Macrophage Colony-Stimulating Factor

“…Although the mechanisms of nonopsonic uptake of GBS by macrophages are not completely understood, lectin-like interactions might be involved (19,21). Nonopsonic recognition of GBS mediated by complement receptor type 3 in mouse peritoneal macrophages and the macrophage cell line PU5-1.8 has been reported (19). We earlier published data showing that OKM1 and M1/70 monoclonal antibodies directed against the ␣ subunit of complement receptor 3 inhibited phagocytosis and killing of GBS by human MDM (15).…”

“…Studies from other laboratories suggest that unopsonized GBS may be phagocytosed by mouse macrophages and macrophage-like cell lines (1,17,19,(21)(22)(23). Although the mechanisms of nonopsonic uptake of GBS by macrophages are not completely understood, lectin-like interactions might be involved (19,21). Nonopsonic recognition of GBS mediated by complement receptor type 3 in mouse peritoneal macrophages and the macrophage cell line PU5-1.8 has been reported (19).…”

Contribution of Mn-Cofactored Superoxide Dismutase (SodA) to the Virulence of Streptococcus agalactiae

“…Pneumonia results from local infections, whereas sepsis and meningitis may be due to the spread of bacteria followed by systemic infection. The humoral and cellular inflammatory responses that contribute to the clearance of S. agalactiae in the host are the opsonization of the bacteria with specific antibodies or with complement, followed by phagocytosis by macrophages or neutrophils (6,17,30). Opsonin-independent phagocytosis mediated by CR3 receptor has also been reported in GBS infection (1).…”

Group B Streptococcal Infections

“…Antibodies to neutrophil Fc receptor III (FcR III) inhibited phagocytosis of opsonized bacteria to an extent exceeding that of CR3. Participation by FcR and complement receptor in phagocytosis of GBS by peritoneal macrophages also has been reported [386]. When complement receptor function was allowed, FcR II participation no longer was requisite for occurrence of phagocytosis.…”