A. Vecchiarelli et al., ROLE OF HUMAN ALVEOLAR MACROPHAGES AS ANTIGEN-PRESENTING CELLS IN CRYPTOCOCCUS-NEOFORMANS INFECTION, American journal of respiratory cell and molecular biology, 11(2), 1994, pp. 130-137
The contribution of human alveolar macrophages (AM) from normal subjec
ts 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 fusio
n. Moreover, the role of AM as antigen-presenting cells was investigat
ed. Cryptococcus-laden AM were co-cultured with autologous T lymphocyt
es and lymphoproliferation was determined; a massive blastogenic respo
nse 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. T
his finding suggests that AM play a key role in the lung as antigen-pr
esenting cells and, through the secretion of IL-1, regulate proliferat
ion 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. n
eoformans infection from the lung.