Effect of Immune Mechanisms on the Pharmacokinetics and Organ Distribution of Cryptococcal Polysaccharide

Cryptococcus neoformans is an encapsulated opportunistic fungus that can cause chronic infections accompanied by high tissue levels of capsular polysaccharide (CPS). CPS or its major component, glucuronoxylomannan (GXM), was administered to mice, and whole-body and tissue levels were measured. The role of monoclonal antibody (MAb), complement, and CD4 T cells in GXM clearance was also examined. These studies demonstrate that CPS is cleared from the blood within days but is retained in the body for weeks; that MAbs of all isotypes examined promote GXM clearance; that MAb-mediated GXM deposition in liver, but not in spleen, is Fc-dependent; that complement enhances IgM-mediated GXM sequestration in liver but not spleen; and that CD4 T cells are not necessary for serum GXM clearance. The results have important implications for the eventual use of MAbs in treatment of cryptococcosis.