Strain variation in antiphagocytic activity of capsular polysaccharides from Cryptococcus neoformans serotype A

Abstract

Strains of Cryptococcus neoformans vary in resistance to phagocytosis in vitro. The binding of isolated capsular polysaccharide (CPS) to a capsule-free mutant of C. neoformans confers resistance to phagocytosis. The importance of capsule composition to differences among strains in susceptibility to phagocytosis was evaluated. CPSs from five strains of C. neoformans serotype A, designated 6, 15, 98, 110, and 145, which had previously been isolated and characterized as to molecular size, composition, and binding properties, were evaluated for relative antiphagocytic potencies. In the presence of 5% normal isologous serum, murine thioglycolate-elicited peritoneal macrophages phagocytized (i.e., attached to or engulfed) 80% of-5Cr-labeled cells of C. neoformans 602, a capsule-free mutant. Added CPS inhibited the uptake of these yeast cells. CPS from strain 110 was most potent, followed in decreasing order of inhibitory activity by CPSs from strains 6, 145, 98, and 15. The presence of 100 ,ug of strain 110 CPS per ml reduced uptake of cells of strain 602 from 80 to 50%. CPS had no effect on the uptake of-5Cr-labeled Saccharomyces cerevisiae. Cells of strain 602 that were preincubated with CPS and then washed were more resistant to phagocytosis than nonpretreated control cells, indicating the importance of bound, not free, CPS. Added CPS did not affect the uptake of wild-type, encapsulated cells of C. neoformans. Addition of endotoxin had no effect on phagocytosis. CPSs from strains of C. neoformans serotype A varied widely in their abilities to inhibit the uptake of capsule-free cells. The antiphagocytic activity of CPS did not correlate with the ability to bind to capsule-free mutants but was somewhat related to the capsule size of the strain from which the CPS was isolated.

Catch me if you can: phagocytosis and killing avoidance by Cryptococcus neoformans

“…In the case of C. neoformans , early studies demonstrated that the capsule inhibited phagocytosis (Kozel & Gotschlich, ). Supporting this role of the capsule, binding of isolated capsular polysaccharide to capsule‐free mutants conferred resistance to phagocytosis (Small & Mitchell, ). Thus, it is believed that the capsule acts as a physical barrier that impairs the recognition of phagocytic receptors with epitopes of the cell wall (Kozel & Gotschlich, ).…”

Virulence factors of medically important fungi

“…A major mechanism by which the capsule seems to enable C. neoformans to subvert host defenses is by presenting a surface not recognized by phagocytes (149,172). Acapsular isolates are readily engulfed by phagocytes, possibly via man-nose and ␤-glucan receptors (56,147,181,247,267). In contrast, in the absence of opsonins, most phagocyte populations will not bind encapsulated strains of C. neoformans (19,147,149,172,181,183).…”

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

“…C. neoformans is unique among the fungi because it has a polysaccharide capsule composed mainly by glucuronoxylomannan (GXM) surrounding the cell that is a major virulence factor (Chang and Kwon‐Chung, 1994; Casadevall and Perfect, 1998; McFadden and Casadevall, 2001). The capsule makes C. neoformans resistant to phagocytosis such that in the absence of opsonins, phagocytic cells do not ingest yeast cells (Mitchell and Friedman, 1972; Kozel and Gotschlich, 1982; Kozel et al ., 1988a; Small and Mitchell, 1989). However, for C. neoformans , Abs also promote phagocytosis through CR3 and CR4 in the absence of C3 by a mechanism that involves a lectin‐like interaction between the capsular polysaccharide and CR3 and CR4 (Dong and Murphy, 1997; Netski and Kozel, 2002; Taborda and Casadevall, 2002).…”

“…When C3 localizes deep inside the capsule, as occurs for cryptococcal cells with large capsules, C3 is not accessible to the receptor and the process is inefficient in promoting phagocytosis (Zaragoza et al ., 2003). Consequently, the efficiency of C‐mediated phagocytosis is critically dependent on the size of the capsule of the C. neoformans strain (Mitchell and Friedman, 1972; Kozel et al ., 1988b; Small and Mitchell, 1989; Yasuoka et al ., 1994; Zaragoza et al ., 2003). Recent studies show that another factor that influences C3 localization is the source of serum, with serum from different mammalian species in different regions of the capsule (Gates and Kozel, 2006).…”