Immunological down-regulation of host defenses in fungal infections.

Fungal pathogens use multiple virulence factors to cause progressive disease. A mechanism that could be regarded as a virulence factor is the fungal pathogen's ability to evade or down-regulate host protective mechanisms. Cryptococcus neoformans is an excellent example of a fungal pathogen that can down-regulate both innate and immune host protective mechanisms. Cr. neoformans is a basidiomycetous yeast-like organism that causes cryptococcosis, a frequently fatal disease in man. This organism produces a capsule that inhibits phagocytosis, and the excess capsular material sloughs off and gets into the bloodstream where it causes L-selectin to shed from the leukocyte surface resulting in reduced migration of leukocytes into the site of infection. Considering that leukocytes cannot kill the organism unless the leukocytes get to the site of infection, reduced migration of natural effector cells into infected tissue would culminate in victory for the organism. Intravascular capsular polysaccharides of Cr. neoformans also induce regulatory T cells that inhibit the protective cell-mediated immune response. Isolates of Cr. neoformans that produce excessive capsular material in the host are highly virulent and a major contribution to their virulence is the ability of the capsular polysaccharide to down-modulate both innate and immune host defensive measures.