INGESTION OF ACAPSULAR CRYPTOCOCCUS-NEOFORMANS OCCURS VIA MANNOSE ANDBETA-GLUCAN RECEPTORS, RESULTING IN CYTOKINE PRODUCTION AND INCREASEDPHAGOCYTOSIS OF THE ENCAPSULATED FORM

Cryptococcus neoformans is a pathogenic yeast and a major cause of opp ortunistic infection in AIDS patients, It is commonly found in an acap sular form in the environment, and infection is likely to occur by inh alation. The lung provides a suitable environment for capsule synthesi s, and once encapsulated, C. neoformans becomes resistant to phagocyto sis, A stable acapsular mutant of the organism is readily ingested by murine macrophages in vitro, indicating entry via constitutively compe tent receptors, We demonstrate In this report that this process is inh ibitable by particles derived from Saccharomyces cerevisiae that are r ich in mannan and beta-glucan, as well as more purified forms of these glycans, Furthermore, ingestion of the acapsular form of C. neoforman s induces a range of proinflammatory cytokines, including tumor necros is factor alpha and granulocyte-macrophage colony-stimulating factor, which, as we have previously shown, enhance ingestion of serum opsoniz ed encapsulated C. neoformans in vitro, We demonstrate that ingestion of the acapsular form of the organism also enhances ingestion of the p athogenic encapsulated form, This is dependent on the production of tu mor necrosis factor alpha and granulocyte-macrophage colony-stimulatin g factor by the macrophages, since addition of neutralizing antibodies to both cytokines inhibited the observed increase in ingestion, Toget her, these data demonstrate that ingestion of acapsular C. neoformans is mediated via mannose and beta-glucan receptors on the macrophage su rface and that this process activates macrophages for enhanced phagocy tosis of the encapsulated form via production of macrophage-derived cy tokines.