The capsule of cryptococcus neoformans passively inhibits phagocytosis of the yeast by macrophages.
We examined the mechanism by which cryptococcal capsular polysaccharide inhibits phagocytosis of Cryptococcus neoformans by macrophages. O-Acetyl and carboxyl groups are major structural features of serotype D polysaccharide. Serotype D capsular polysaccharide or encapsulated whole cryptococci were de-O-acetylated by alkaline hydrolysis with 0.1 M NaOH. Carboxyl groups were reduced by treatment with 1-ethyl-3(3-dimethylaminopropyl)carbodiimide followed by reduction with sodium borohydride. De-O-acetylated or carboxyl-reduced polysaccharides had phagocytosis-inhibiting properties that did not differ appreciably from the untreated polysaccharide; thus, neither the O-acetyl nor the carboxyl groups were essential phagocytosis-inhibiting determinants. Antiserum specific for these noninhibitory groups was obtained by adsorption of cryptococcal antiserum with de-O-acetylated or carboxyl-reduced whole cells to produce antiserum enriched respectively with antibody specific for the O-acetyl and carboxyl groups. These adsorbed antisera showed opsonic activity for the untreated yeast that was similar to the unadsorbed antiserum when these antisera were compared at identical levels of precipitating antibody. We also examined the ability of Fab' fragments of opsonic IgG to reduce the amount of anticapsular IgG needed to opsonize the yeast. No synergy was noted between Fab' fragments and undigested IgG in opsonization. These results are consistent with a passive mechanism for inhibition of phagocytosis. The capsule does not directly modulate phagocytic function, but instead, presents a surface that is not recognized by the phagocyte. This absence of recognition is corrected by opsonizing antibody specific for any surface determinant on the capsule.
D000818:Animals; D000908:Antibodies, Fungal; D003454:Cryptococcus / Q000276:immunology*; D003455:Cryptococcus neoformans / Q000276:immunology* / Q000648:ultrastructure; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D009895:Opsonin Proteins; D010587:Phagocytosis; D011134:Polysaccharides / Q000276:immunology; D013329:Structure-Activity Relationship
D000908:Antibodies, Fungal; D007140:Immunoglobulin Fab Fragments; D009895:Opsonin Proteins; D011134:Polysaccharides