Antibody to the Type 3 Capsule Facilitates Immune Adherence of Pneumococci to Erythrocytes and Augments Their Transfer to Macrophages

Abstract

Streptococcus pneumoniae has been shown to bind to erythrocytes via a process called immune adherence. This adherence and the subsequent transfer of pneumococci from erythrocytes to macrophages are both dependent on complement C3 deposition onto the pneumococcal surface. The observation that anti-capsule antibody increases C3 deposition on the pneumococcal capsule indicated that anti-capsule antibody may also facilitate the clearance of pneumococci through immune adherence. Using pneumococcal strain WU2 (capsule type 3) and its nonencapsulated mutant JD908, we found that monoclonal antibody (MAb) to type 3 capsule increases complement C3, C1q, and C4 deposition on WU2 and enhanced the immune adherence of WU2 to erythrocytes. The MAb to type 3 capsule also enhanced the transfer of WU2 from erythrocytes to macrophages. Moreover, the transfer reaction was inhibited by preincubating macrophages with anti-CR3 or anti-Fc␥RIII/II MAb, indicating that CR3 and Fc␥RIII/II on macrophages mediate this process. The transfer reactions of JD908 (opsonized with complement) and WU2 (opsonized with complement plus MAb to type 3 capsule) were similarly inhibited by anti-CR3 MAb, but only the latter was inhibited by anti-Fc␥RIII/II MAb. This finding indicates that although complement and the macrophage receptor CR3 are essential for the transfer reaction, if antibody is present it can further enhance the transfer reaction through a process dependent on Fc␥RIII/II. Using pre-and postvaccination sera of people immunized with the 23-valent pneumococcal polysaccharide vaccine, we confirmed that human anti-capsule antibodies are also able to increase the immune adherence of pneumococci and their transfer to macrophages.

Aggregation of Streptococcus pneumoniae by a Pneumococcal Capsular Polysaccharide-Specific Human Monoclonal IgM Correlates with Antibody Efficacy In Vivo

“…In light of these tenets and previous work which demonstrated that A7 is not opsonic in vitro (14) and requires C3 to mediate protection in mice (10), our data suggest that the mechanism by which A7 mediates protection in vivo is by promoting C3 deposition on the ST3 capsule. Clearance of C3-opsonized bacteria is enhanced in vivo (4,5), and immune adherence of C3-opsonized bacteria to red blood cells via complement receptors is thought to enhance intravascular clearance to the reticuloendothelial system (20,32,33). The phenomenon of immune adherence has been reported for PPS-specific IgG, but to our knowledge, it has not been demonstrated for IgM.…”

Immunization with Pneumococcal Polysaccharide Serotype 3 and Lipopolysaccharide Modulates Lung and Liver Inflammation during a Virulent Streptococcus pneumoniae Infection in Mice

“…The ability of IgM in serum to bind to pneumococci was determined by an in vitro IgM-binding assay as described previously (11). Bacteria frozen stock was washed twice in PBS and centrifuged at 4,000 ϫ g for 6 min.…”

A Serotype 3 Pneumococcal Capsular Polysaccharide-Specific Monoclonal Antibody Requires Fcγ Receptor III and Macrophages To Mediate Protection against Pneumococcal Pneumonia in Mice

“…The ST3 S. pneumoniae WU2 strain was grown in tryptic soy broth (TSB) to mid-log phase as described previously (49). WU2 has been used extensively to study the host response to and survival after infection with ST3 in mice (6,26,30,37,48,49,54). Purified PPS3, isolated from strain 6303 and obtained from the American Type Culture Collection, was used for enzyme-linked immunosorbent assay (ELISA)-based analyses of MAb binding.…”