Immunological down-regulation of host defenses in fungal infections

Fungal pathogens use multiple virulence factors to cause progressive diseas e. A mechanism that could be regarded as a virulence factor is the fungal p athogen's ability to evade or down-regulate host protective mechanisms. Cry ptococcus neoformans is an excellent example of a fungal pathogen that can down-regulate both innate and immune host protective mechanisms. Cr. neofor mans is a basidiomycetous yeast-like organism that causes cryptococcosis, a frequently fatal disease in man. This organism produces a capsule that inh ibits phagocytosis, and the excess capsular material sloughs off and gets i nto the bloodstream where it causes L-selectin to shed from the leukocyte s urface resulting in reduced migration of leukocytes into the site of infect ion. Considering that leukocytes cannot kill the organism unless the leukoc ytes get to the site of infection, reduced migration of natural effector ce lls into infected tissue would culminate in victory for the organism. Intra vascular capsular polysaccharides of Cr. neoformans also induce regulatory T cells that inhibit the protective cell-mediated immune response. Isolates of Ca 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.