Abstract
Immunosuppressed patients are frequently afflicted with severe mycoses caused by opportunistic fungal pathogens. Besides being a commensal, colonizing predominantly skin and mucosal surfaces, Candida albicans is the most common human fungal pathogen. Mast cells are present in tissues prone to fungal colonization being expectedly among the first immune cells to get into contact with C. albicans. However, mast cell-fungus interaction remains a neglected area of study. Here we show that human mast cells mounted specific responses towards C. albicans. Collectively, mast cell responses included the launch of initial, intermediate and late phase components determined by the secretion of granular proteins and cytokines. Initially mast cells reduced fungal viability and occasionally internalized yeasts. C. albicans could evade ingestion by intracellular growth leading to cellular death. Furthermore, secreted factors in the supernatants of infected cells recruited neutrophils, but not monocytes. Late stages were marked by the release of cytokines that are known to be anti-inflammatory suggesting a modulation of initial responses. C. albicans-infected mast cells formed extracellular DNA traps, which ensnared but did not kill the fungus. Our results suggest that mast cells serve as tissue sentinels modulating antifungal immune responses during C. albicans infection. Consequently, these findings open new doors for understanding fungal pathogenicity.
Highlights
Virtually unexplored[9,10,11,12]
Degranulation is a putative mechanism mast cells may employ to respond to C. albicans infection
Mast cells degranulated and released β -hexosaminidase in response to C. albicans after 1 h of infection in a dose-dependent manner (Fig. 1A)
Summary
Virtually unexplored[9,10,11,12]. Interestingly, mast cells express molecules, for instance inflammatory cytokines, myeloid-attracting chemokines, and pattern recognition receptors that were demonstrated to be involved in antifungal responses in other cells. Activation of C-type lectin receptors, such as dectin 1, by fungal components results in mast cell activation[18,19] This suggests a possible involvement of mast cells in antifungal immunity. Specific ligands for such receptors can activate mast cells causing release of reactive oxygen species[20] and different vasoactive mediators, for instance histamine, prostaglandins, leukotrienes, and tryptase, which are injurious to the microbes[21]. While most of these mediators promote inflammation, they are in addition responsible to recruit other immune cells[22,23]. Our work contributes to the understanding of the role of mast cells in modulating the innate immune response against opportunistic pathogenic fungi
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