Downregulation by cryptococcal polysaccharide of tumor necrosis factor alpha and interleukin-1β secretion from human monocytes

Abstract

The regulation by Cryptococcus neoformans encapsulation of interleukin 1β (IL-1β) and tumor necrosis factor alpha (TNF-α) production by human monocytes was investigated. By using encapsulated and acapsular C. neoformans, we demonstrated that both strains induce cytokine production, although the acapsular strain was a better stimulator than the thinly encapsulated strain. The cytokine levels produced by cells stimulated by the two strains were lower and followed a different kinetic than those stimulated by lipopolysaccharide (LPS). Purified capsular polysaccharide inhibits TNF- α secretion induced by LPS or acapsular C. neoformans. In contrast, no regulatory effect on IL-1β was observed when LPS was used. The secretory response of these cytokines follows different pathways of macrophage activation; in fact, complete inhibition of TNF-α does not affect IL-1β production and vice versa. These data indicate that purified capsular polysaccharide of C. neoformans could contribute to the in vivo progress of cryptococcosis by suppressing cytokine production of macrophages and suggest that a therapeutic approach to address the suppressive effect of cryptococcal polysaccharide could be devised.