Ingestion of acapsular Cryptococcus neoformans occurs via mannose and beta-glucan receptors, resulting in cytokine production and increased phagocytosis of the encapsulated form

Abstract

Cryptococcus neoformans is a pathogenic yeast and a major cause of opportunistic infection in AIDS patients. It is commonly found in an acapsular form in the environment, and infection is likely to occur by inhalation. The lung provides a suitable environment for capsule synthesis, and once encapsulated, C. neoformans becomes resistant to phagocytosis. A stable acapsular mutant of the organism is readily ingested by murine macrophages in vitro, indicating entry via constitutively competent receptors. We demonstrate in this report that this process is inhibitable by particles derived from Saccharomyces cerevisiae that are rich in mannan and ␤-glucan, as well as more purified forms of these glycans. Furthermore, ingestion of the acapsular form of C. neoformans induces a range of proinflammatory cytokines, including tumor necrosis factor alpha and granulocyte-macrophage colony-stimulating factor, which, as we have previously shown, enhance ingestion of serum-opsonized encapsulated C. neoformans in vitro. We demonstrate that ingestion of the acapsular form of the organism also enhances ingestion of the pathogenic encapsulated form. This is dependent on the production of tumor necrosis factor alpha and granulocyte-macrophage colony-stimulating factor by the macrophages, since addition of neutralizing antibodies to both cytokines inhibited the observed increase in ingestion. Together, these data demonstrate that ingestion of acapsular C. neoformans is mediated via mannose and ␤-glucan receptors on the macrophage surface and that this process activates macrophages for enhanced phagocytosis of the encapsulated form via production of macrophage-derived cytokines.

Enhancement of IL-8 production from human monocytic and granulocytic cell lines, THP-1 and HL-60, stimulated with Malassezia furfur

“…It is thought that the cell wall of M. furfur is composed of mannan and L-glucan, although their structures were not examined in detail [18]. We found, however, that M. furfur contains (1C3)-and (1C6)-L-D-glucans in cell wall by using 13 C-NMR (unpublished data). Thus the cell wall L-glucan would participate in the expression of IL-8 mRNA from phagocytes and subsequent induction of in£ammatory responses.…”

Contribution of tumour necrosis factor-alpha (TNF-α) in host defence mechanism against Cryptococcus neoformans

“…In contrast, the C. neoformans strain used in the study of Collins & Bancroft [37], although not described in detail, appears to be less virulent, since the number of injected yeast cells was 10 times higher than that used in our study. Despite the higher dose, it did not result in a lethal infection [37,38], and induced the expression of TNF-mRNA in vitro by macrophages [38]. These results indicate that TNFis copiously produced in infected sites and plays an important protective role.…”

In vitromodulation of human keratinocyte pro- and anti-inflammatory cytokine production by the capsule ofMalasseziaspecies

“…Parallels were made to the polysaccharide-rich capsule of Cryptococcus neoformans, shown to confer antiphagocytic properties and downregulation of proinflammatory cytokine (IL-1b and TNF-a) production by monocytes (Kozel et al, 1988;Vecchiarelli et al, 1995). Uptake of acapsular C. neoformans by murine macrophages and induction of IL-1b, TNF-a and GM-CSF was controlled by mannose and b-glucan receptors and it was concluded that the capsule masks carbohydrate residues in the yeasts cell walls (Cross & Bancroft, 1995) in a similar way as the lipid capsule of Malassezia is speculated to in this study. Unfortunately, very little research has been performed to determine the composition of Malassezia cell wall, but it is known to contain high proportions of carbohydrate (Hechemy & Vanderwyk, 1968;Thompson & Colvin, 1970).…”