Polysaccharide antigens of the capsule of Cryptococcus neoformans

Abstract

The major significance of the capsular polysaccharide of C. neoformans is its role in potentiating opportunistic infections by the yeast. It has the ability to exert a broad spectrum of influences on the immune response, from activation of phagocytic cells and complement components of the alternative pathway, to the induction of specific antibody, T-suppressor cells, DTH responses, and cytokines (51). These biological properties along with the serotype specificities are all determined by the physical properties and chemical structures of the polysaccharide antigens that compose the capsule. There is evidence not only for an association of lethal infections with serotype A in patients with advanced AIDS (34, 56), but also for a role for the capsule in directly influencing the infection of CD4+ cells by HIV (57). Together, these phenomena raise intriguing questions about the possible connection between the chemistry of these capsular antigens and cryptococcal infections in AIDS patients. One speculation is that AIDS creates the optimal physiological conditions for the establishment and spread of cryptococcosis. It has been observed that during the progression of AIDS there is a shift towards a T-2 response (14). This could lead to conditions that would inhibit the cellular immune responses that block dissemination of cryptococcal infections. Thus, an important consideration in the application of vaccine or immune modulation therapies in the treatment of cryptococcosis in AIDS victims would be the design of vaccines that could boost the T-1 immune response. It has been shown that the form and dose of an antigenic challenge can influence the induction of a T-1 or T-2 immune response (61). Recently, Murphy has reported that gamma interferon and interleukin 2 are up-regulated in the spleens of mice that produce anticryptococcal TDH and TAMP cells in response to immunogenic doses of cryptococcal culture filtrate antigen given with Freund's complete adjuvant (49). Perhaps purified cryptococcal antigens (e.g., MP) conjugated to an appropriate carrier or adjuvant could be used in therapeutic strategies to limit cryptococcosis in immunocompromised individuals. Future investigations of virulence and pathogenicity in the context of defined polysaccharide antigens from encapsulated strains of C. neoformans will contribute to a better understanding of the regulation of cryptococcal infection and immunity at the cellular and molecular levels.(ABSTRACT TRUNCATED AT 400 WORDS)

The ABC transporter-encoding geneAFR1affects the resistance ofCryptococcus neoformansto microglia-mediated antifungal activity by delaying phagosomal maturation

“…Specific virulence factors of C. neoformans, including polysaccharide capsule (Bhattacharjee et al, 1984;Cherniak & Sundstrom, 1994), melanin (Shaw & Kapica, 1972) or mannitol production (Wong et al, 1990), superoxidase dismutase (Jacobson et al, 1994), proteases (Brueske, 1986;Blasi et al, 2004), phospholipase B and lysophospholipase (Chen et al, 1997a, b), have been described; among all, capsule formation and melanin production appear as crucial elements to elude host defences at the brain level (Blasi et al, 1992(Blasi et al, , 1995a. Recently, the antifungal resistance 1 (AFR1) gene has been identified and characterized (Posteraro et al, 2003;Sanguinetti et al, 2006): it encodes an ATP binding cassette transporter protein, involved in the in vitro resistance to fluconazole (Posteraro et al, 2003).…”

Application of proton nuclear magnetic resonance spectroscopy to the study ofCryptococcusand cryptococcosis

“…GXMs are partially 6-O-acetylated. The GXM structure of all serotypes has been studied by NMR spectroscopy (Skelton et al, 1991;Cherniak & Sundstrom, 1994;Bacon et al, 1996;Sheng & Cherniak, 1997). Although exact molar ratios of Xyl/Man/ GlcA and substituent dispositions were initially assigned to each of the four serotypes, it is now known that this is an oversimplification (Cherniak et al, 1998).…”

TheCryptococcus neoformans cap10 andcap59 mutant strains, affected in glucuronoxylomannan synthesis, differentially activate human dendritic cells

“…This capsule enables the yeast-like fungus to survive the harsh environment of the human body by immune evasion and by preventing killing through phagocytosis by macrophages (Perfect et al, 1998;Murphy, 1999). The capsule consists mainly of the polysaccharides glucuronoxylomannan and galactoxylomannan at a mass ratio of about 10 : 1 (Cherniak et al, 1982(Cherniak et al, , 1988Cherniak & Sundstrom, 1994). Mannoproteins account for a minor fraction of the capsule (Reiss et al, 1985).…”