Localization of complement component 3 on Streptococcus pneumoniae: anti-capsular antibody causes complement deposition on the pneumococcal capsule

Abstract

We have previously shown that complement component 3 (C3) deposited onto encapsulated Streptoc-occius pnzeiotuttiiae by anti-capsular antibody (Ab) is a more efficient opsonin in vitro and in vivo than C3 deposited by anti-cell wall Ab (Brown et al., J. Clin. Invest. 69:85-98, 1982). In the present study, we explored the cellular location of C3b molecules that differ in opsonic efficiency by using avidin-ferritin to localize biotinylated Ab and C3 molecules on S. pnleiuitiolniae for electron microscopy. Anti-cell wall Ab and C3b molecules deposited by this Ab on unencapsulated S. pneimsoniae were localized to S. pnteiottiae cell walls. Anti-capsular Ab and C3b deposited by this Ab were seen in clusters on encapsulated S. pneuinoniiae at a distance from the cell wall. However, no avidinferritin staining of encapsulated S. pneitu,notn(ie was seen on incubation with biotinyl-anti-cell wall Ab. biotinylated C3 fixed by anti-cell wall Ab, or nonimmune serum containing biotinyl-C3. In each case, uptake of the biotinylated component was proven by radioactivity measurements, since biotinylated Ab and

The efficacy of complement‐mediated phagocytosis of Cryptococcus neoformans is dependent on the location of C3 in the polysaccharide capsule and involves both direct and indirectC3‐mediated interactions

“…The internal deposition of complement could be also related to the different density of the capsule, with some being less compact at the edge and thus allowing the deposition of complement inside the capsule 36. Although different encapsulated microbial species can bind C3 in different cellular locations 37, our results show a change in C3 localization for one organism depending on capsule volume.…”

Monoclonal antibodies can affect complement deposition on the capsule of the pathogenic fungus Cryptococcus neoformans by both classical pathway activation and steric hindrance

“…There are previous reports in the literature that indicate that Abs change C3 localization but we note that those findings involved differences in C3 deposition mediated by Abs that bound to different Ags. For example, in S. pneumoniae, Abs to the capsule or to the cell wall promoted C3 binding to the capsule or the cell wall respectively (Brown et al ., 1983). Hence, in that system Ab‐mediated differences in C3 localization were caused by Abs that bound to different antigens.…”

“…Antibodies affect C3 localization on microbial capsules by activating the classical pathway. For example, in the case of Streptococcus pneumoniae , Abs to the capsule and cell surface promote deposition of C3 on the capsule and cell surface respectively (Brown et al ., 1983), but only Abs to the capsule increase adherence (Brown et al ., 1982). In contrast, for Neisseria gonorrhoeae , blocking non‐protective Abs promote the deposition of C3 in the microbial surface at sites that do not promote serum killing (Joiner et al ., 1985).…”

The Regulation of Pulmonary Immunity

“…Nontype-specific antibodies to S . pneumoniae are made during infection, including antibodies to cell wall components (Brown et al, 1983), surface protein A (Szu et al, 1983), and the F polysaccharide (Au and Eisenstein, 1981). In general, most animal studies indicate that these latter antibodies play a minimal role in providing effective protection against infection by S .…”

“…In general, most animal studies indicate that these latter antibodies play a minimal role in providing effective protection against infection by S . pneumoniae (Szu et al, 1986;Brown et al, 1983).…”