Glucuronoxylomannan-mediated interaction of Cryptococcus neoformans with human alveolar cells results in fungal internalization and host cell damage

Binding of Glucuronoxylomannan to the CD14 Receptor in Human A549 Alveolar Cells Induces Interleukin-8 Production

“…Untreated human cells or an A549 population that was pretreated with LPS (10 g/ml) for 1 h was incubated with C. neoformans under previously established conditions (2). The index of association between cryptococci and alveolar cells was measured as the reactivity of A549 cells with MAb 18B7 in flow cytometry assays (2), which showed that the efficacy of the interaction of cryptococci with untreated cells was higher than that observed with LPS-treated epithelia (Fig.…”

“…Infections are acquired by inhalation of desiccated cells, which are available in the environment as basidiospores or poorly encapsulated yeasts. Inhaled cells are deposited in the alveolar space, where they are ingested by macrophages (24) and interact with epithelial cells (2,7,8). An effective interaction of C. neoformans with epithelial alveolar cells is probably essential for the establishment of pulmonary infection.…”

“…Once C. neoformans becomes established in the lung, it proliferates locally and causes a primary lesion that is usually contained by granuloma formation (10,24). Two components of C. neoformans that are important for adhesion to human type II alveolar epithelial cells are phospholipase B (8) and glucuronoxylomannan (GXM) (2).…”

“…GXM was purified from strain T 1 -444 of C. neoformans (serotype A) by following standard methods (5) and incubated with A549 cells (100 g/ml) for 1 h at 37°C (2). Binding of GXM to host cells was confirmed by immunofluorescence with the GXM-binding monoclonal antibody (MAb) 18B7 (3) (Fig.…”

Antifungal activity of the naphthoquinone beta-lapachone against disseminated infection with Cryptococcus neoformans var. neoformans in dexamethasone-immunosuppressed Swiss mice

“…Patients infected with HIV, cancer patients, diabetics, patients submitted to transplants or invasive procedures, or people taking corticosteroids are especially susceptible to the disease. Primary cryptococcal infection starts in the lungs and commonly disseminates to several organs (2). However, the yeast shows tropism for the central nervous system, where it survives and proliferates, causing meningitis and meningoencephalitis, both of which can be fatal if not treated properly (3).…”