ENCAPSULATION OF CRYPTOCOCCUS-NEOFORMANS REGULATES FUNGICIDAL ACTIVITY AND THE ANTIGEN PRESENTATION PROCESS IN HUMAN ALVEOLAR MACROPHAGES

Our previous studies have shown that unstimulated alveolar macrophages (AM) play a pre-dominant role as antigen-presenting cells in Cryptoco ccus neoformans infections, while the function as effector cells seems to be of minor relevance. The present study focuses on the role of en capsulation of C. neoformans on fungicidal activity and the antigen pr esentation process of AM. Fungicidal activity in unstimulated AM occur s to a higher degree when the acapsular strain is employed, but this i s impaired compared with other natural effecters, such as peripheral b lood monocytes (PBM) and polymorphonuclear (PMN) cells. Cryptococcus-l aden AM also induce a higher proliferative response in autologous CD4( +) lymphocytes when the acapsular strain is used compared with encapsu lated yeast. The enhanced blastogenic response is, in part, ascribed t o an augmented IL-2 production by T cells. In addition, higher levels of interferon-gamma (IFN-gamma), but not IL-4, are produced by the res ponding T cells, when the acapsular strain is used compared with the e ncapsulated yeast. Moreover, IFN-gamma is able to induce fungicidal ac tivity in AM against the encapsulated yeast and augments killing activ ity of the acapsular strain. This phenomenon is not mediated by nitric oxide production, but is correlated with an enhancement of fungicidal activity of cytoplasmic cationic proteases. We speculate that encapsu lation of C. neoformans could downregulate the development of the immu ne response mediated by Cryptococcus-laden AM at lung level.