Antibody-dependent Killing of Cryptococcus neoformans by Human Peripheral Blood Mononuclear Cells

Abstract

CRYPTOCOCCOSIS is a systemic fungus infection caused by the encapsulated yeast-like fungus, Cryptococcus neoformans. It has been suggested that alterations in cellular host defence mechanisms increase susceptibility to infection with this organism^1,2. In vitro studies suggest that human peripheral blood neutrophils and monocytes can ingest and kill cryptococci^3,4. There is, however, a wide range of killing in cells from different normal subjects (21–89%), and no apparent defect in cells from patients with cryptococcosis³. This makes it unlikely that peripheral blood neutrophils or monocytes play a decisive role in determining susceptibility to cryptococcosis in individual patients. In other in vitro studies, activated macrophages derived from human peripheral blood monocytes not only failed to kill cryptococci, but provided a preferentially favourable medium for intracellular growth of the fungus⁵. These studies, as well as the known histopathology of cryptococcal lesions, suggest that many of the organisms, particularly large capsule forms, are extracellular and so not subject to the intracellular killing mechanisms of phagocytes. Anti-cryptococcal antibody, with or without complement, does not kill cryptococci in the absence of leukocytes³. I therefore investigated the possible existence of a non-phagocytic cellular killing mechanism.