Mechanisms of Native and Acquired Resistance to Infection with Cryptococcus Neoformans

Abstract

The mechanisms of resistance mustered by the host to ward off infection with Cryptococcus neoformans mirror many of the classical responses shown with intracellular bacteria. Thus, the administration of an appropriate cellular antigen can protect animals from an otherwise lethal infection in the absence of demonstrable humoral antibody. It is now known that this resistance most probably can be transferred both by “immune” lymphocytes and macrophages.³⁶ A similar effect can be obtained with endotoxin, but limitation of the infection in this case apparently requires the presence of circulating antibody directed against the capsule. Neutralization of the adverse effects of extracellular polysaccharide on chemotaxis and pinocytosis is the most plausible explanation.

In spite of the formidable natural protection afforded by the respiratory apparatus, the ultimate mediators in defense against C. neoformans must be the phagocytes, most particularly the macrophages. Although the metabolic activity of fully activated macrophages has never been the subject of a detailed study, basic proteins isolated from both PMN and mononuclear phagocytes can kill the fungus, both in vitro and apparently also in vivo, in appropriate intra and extracellular situations.