Role of human alveolar macrophages as antigen-presenting cells in Cryptococcus neoformans infection

Abstract

The contribution of human alveolar macrophages (AM) from normal subjects in Cryptococcus neoformans infection was investigated. AM were able to efficiently phagocytize the fungus after opsonization, but killing activity did not occur at an effector-to-target ratio of 10:1 in a 6-h incubation since there was an inhibition of phagosome-lysosome fusion. Moreover, the role of AM as antigen-presenting cells was investigated. Cryptococcus-laden AM were co-cultured with autologous T lymphocytes and lymphoproliferation was determined; a massive blastogenic response of alpha/beta TCR-bearing T lymphocytes was observed. The response started after 1 day of co-culture and was triggered and regulated by IL-1 produced by AM in response to C. neoformans. Finally, the antigen-presentation process was associated with HLA class II DR molecules. This finding suggests that AM play a key role in the lung as antigen-presenting cells and, through the secretion of IL-1, regulate proliferation and activation of T lymphocytes, which are important in mediating pulmonary clearance. We speculate that in immunodepressive conditions, the impairment of AM functions could contribute to the spread of C. neoformans infection from the lung.