Micafungin Enhances the Human Macrophage Response to Candida albicans through β-Glucan Exposure

Abstract

Micafungin belongs to the antifungal family of echinocandins, which act as noncompetitive inhibitors of the fungal cell wall β-1,3-d-glucan synthase. Since is the most prevalent pathogenic fungus in humans, we study the involvement of micafungin in the modulation of the inflammatory response developed by human tissue macrophages against The MIC for micafungin was 0.016 μg/ml on the SC5314 standard strain. Micafungin induced a drastic reduction in the number of exponential SC5314 viable cells, with the fungicidal effect being dependent on the cellular metabolic activity. Notably, micafungin also caused a structural remodelling of the cell wall, leading to exposure of the β-glucan and chitin content on the external surface. At the higher doses used (0.05 μg/ml), the antifungal also induced the blowing up of budding yeasts. In addition, preincubation with micafungin before exposure to human tissue macrophages enhanced the secretion of tumor necrosis factor alpha (TNF-α), interleukin-17A (IL-17A), and IL-10 cytokines. Our results strongly suggest that in treatment with micafungin, in addition to having the expected toxic antifungal effect, it potentiates the immune response, improving the interaction and activation of human macrophages, probably through the unmasking of β-glucans on the cell wall surface.

Sodium houttuyfonate attenuates dextran sulfate sodium associated colitis precolonized withCandida albicansthrough inducing β-glucan exposure

“…4C). As demonstrated, classical antifungals such as caspofungin and micafungin can unmask buried β‐glucan in C. albicans cell wall with elevated proinflammatory cytokine TNF‐α production and subsequently activate innate immune respone 31,32 . Based on the findings that SH induces β‐glucan exposure with increased TNF‐α, we suppose that SH mediates the activation of intestinal macrophage and subsequent C. albicans elimination.…”

Sodium houttuyfonate enhances the mono-therapy of fluconazole on oropharyngeal candidiasis (OPC) through HIF-1α/IL-17 axis by inhibiting cAMP mediated filamentation in Candida albicans-Candida glabrata dual biofilms

“…Secondly, anoxia can assist C. albicans to evade immune surveillance by cell wall masking of β-glucan, a pathogen associated molecular pattern (PAMP) that could be recognized by dectin-1 on the surface of immune cells [ 69 , 70 ]. However, increasing evidence demonstrates that several drugs can induce exposure of the cell wall β-glucan and activate the innate immune response to invaded C. albicans [ 71 , 72 ]. Fortunately, Arnab et al and our group found that both FLU and SH had the ability of inducing cell wall β-glucan exposure in C. albicans [ 62 , 73 ].…”

Potential of Sulforaphane and Broccoli Membrane Vesicles as Regulators of M1/M2 Human Macrophage Activity

“…Phagocytosis assays performed with live yeast revealed similar results, although in this case, unloaded broccoli membrane vesicles were also able to reduce phagocytosis compared with untreated control cells. The different set of interactions that can take place between PAMPs expressed in the yeast cell wall, such as β-glucans, with its specific PRR exposed on the macrophage cell surface, such as dectin-1 [ 46 ], could contribute to the differences found. Consistent with our results, it has been reported that SFN treatment was able not only to reduce the production of proinflammatory cytokines but also to suppress the antibody-independent phagocytic and chemotactic migratory abilities of human peripheral blood monocytes [ 47 ]; and to reduce the phagocytosis and microbicidal activity of human M1 monocyte-derived macrophages and THP-1 derived macrophages on Streptococcus aureus and Escherichia coli [ 45 ].…”