Phospholipids Trigger Cryptococcus neoformansCapsular Enlargement during Interactions with Amoebae andMacrophages

摘要

A remarkable aspect of the interaction of Cryptococcus neoformans with mammalian hosts is a consistent increase in capsule volume. Given that many aspects of the interaction of C. neoformans with macrophages are also observed with amoebae, we hypothesized that the capsule enlargement phenomenon also had a protozoan parallel. Incubation of C. neoformans with Acanthamoeba castellanii resulted in C. neoformans capsular enlargement. The phenomenon required contact between fungal and protozoan cells but did not require amoeba viability. Analysis of amoebae extracts showed that the likely stimuli for capsule enlargement were protozoan polar lipids. Extracts from macrophages and mammalian serum also triggered cryptococcal capsular enlargement. C. neoformans capsule enlargement required expression of fungal phospholipase B, but not phospholipase C. Purified phospholipids, in particular, phosphatidylcholine, and derived molecules triggered capsular enlargement with the subsequent formation of giant cells. These results implicate phospholipids as a trigger for both C. neoformans capsule enlargement in vivo andexopolysaccharide production. The observation that the incubation of C.neoformans with phospholipids led to the formation of giant cellsprovides the means to generate these enigmatic cells in vitro.Protozoan- or mammalian-derived polar lipids could represent a danger signal forC. neoformans that triggers capsular enlargement as anon-specific defense mechanism against potential predatory cells. Hence,phospholipids are the first host-derived molecules identified to triggercapsular enlargement. The parallels apparent in the capsular response ofC. neoformans to both amoebae and macrophages provideadditional support for the notion that certain aspects of cryptococcal virulenceemerged as a consequence of environmental interactions with other microorganismssuch as protists.