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)