The immunology of cryptococcal disease.

Cryptococcus neoformans is a ubiquitous fungus found in the soil. Upon inhalation, a complex, incompletely understood series of host responses begins that determines whether the infection will be controlled or will progress to local or disseminated disease. Local pulmonary disease may be asymptomatic or may pursue a subacute course with mild pulmonary symptoms and systemic complaints suggestive of tumor. In the compromised host, however, symptomatic pulmonary disease is often the harbinger of systemic dissemination. Early host responses include phagocytosis by polymorphonuclear leukocytes aided by complement activation which provides opsonins. Lymphocytes are activated to produce lymphokines which may enhance macrophage phagocytosis and intracellular killing of ingested cryptococci. Other lymphocytes may function as natural killer-like cells or inhibit the growth of the fungus. Production of antibody further facilitates phagocytosis by both polymorphonuclear leukocytes (PMN) and monocytes (MC). In the presence of antibody, both PMN and MC demonstrate antibody-dependent cell-mediated cytotoxicity. The combination of humoral and cell-mediated immunity in normal hosts appears to provide excellent protection against disseminated infection as evidence by the rarity of disease in exposed individuals with positive skin tests. By contrast, the frequency of cryptococcal disease in steroid-treated individuals, allograft recipients, and AIDS victims highlight the importance of T lymphocyte dependent host defenses. In view of compelling in vitro evidence for the importance of humoral responses, the infrequency of cryptococcal disease in patients with gammopathies remains a puzzle.