Mast Cells Kill Candida albicans in the Extracellular Environment but Spare Ingested Fungi from Death

Abstract

Mast cells (MCs) reside in tissues that are common targets of Candida spp. infections, and can exert bactericidal activity, but little is known about their fungicidal activity. MCs purified from rat peritoneum (RPMC) and a clinical isolate of C. albicans, were employed. Ingestion was evaluated by flow cytometry (FACS) and optical microscopy. The killing activity was assayed by FACS analysis and by colony forming unit method. RPMC degranulation was evaluated by β-hexosaminidase assay and phosphatidylserine externalization by FACS. Phagocytosing RPMC were also analyzed by transmission electron microscopy. Herein, we show that the killing of C. albicans by RPMC takes place in the extracellular environment, very likely through secreted granular components. Ultrastructural analysis of the ingestion process revealed an unusual RPMC-C. albicans interaction that could allow fungal survival. Our findings indicate that MCs have a positive role in the defense mechanism against Candida infections and should be included among the cell types involved in host-defense against this pathogen.

NOD1 and NOD2 Interact with the Phagosome Cargo in Mast Cells: A Detailed Morphological Evidence

“…Conversely, the bacteria or killed fungi-containing vacuoles appear to assume a conventional compact appearance [21][22][23], which strongly resembles that seen in rat peritoneal macrophages [21]. These phagosomes frequently merge with secretory granules suggesting an active intra-phagosomal bactericidal activity against opsonized bacteria [21,24]. We noted that, in many instances, the microorganisms were imprisoned in very tight vacuoles, their surface showing a continuous interaction with the phagosome membrane.…”

“…Furthermore, the ultrastructural analysis of the ingestion process revealed that the C. albicans-containing phagosome assumes a peculiar structure, which is compatible with a safe haven for the parasite [21]. Conversely, the bacteria or killed fungi-containing vacuoles appear to assume a conventional compact appearance [21][22][23], which strongly resembles that seen in rat peritoneal macrophages [21]. These phagosomes frequently merge with secretory granules suggesting an active intra-phagosomal bactericidal activity against opsonized bacteria [21,24].…”

“…Hence, the meaning of the phagocytic process in mast cells remains unclear. Recently, we showed that the fungicidal activity of these cells against Candida albicans is carried out mainly in the extracellular environment through the release of granule components, such as LL37, regardless of the extent of ingestion [21]. Furthermore, the ultrastructural analysis of the ingestion process revealed that the C. albicans-containing phagosome assumes a peculiar structure, which is compatible with a safe haven for the parasite [21].…”

“…Recently, we showed that the fungicidal activity of these cells against Candida albicans is carried out mainly in the extracellular environment through the release of granule components, such as LL37, regardless of the extent of ingestion [21]. Furthermore, the ultrastructural analysis of the ingestion process revealed that the C. albicans-containing phagosome assumes a peculiar structure, which is compatible with a safe haven for the parasite [21]. Conversely, the bacteria or killed fungi-containing vacuoles appear to assume a conventional compact appearance [21][22][23], which strongly resembles that seen in rat peritoneal macrophages [21].…”

“…This event could increase the relevance of this process in MC, which are not generally considered to be true professional phagocytes [21,24,33,34], but could instead exploit the ingestion process to trigger the synthesis of pro-inflammatory mediators.…”