Abstract:Sporotrichosis is a human and animal fungal infection distributed worldwide that is caused by the thermodimorphic species of the Sporothrix pathogenic clade, which includes Sporothrix brasiliensis, Sporothrix schenckii, and Sporothrix globosa. The cell wall composition and the immune response against the Sporothrix species have been studied mainly in S. brasiliensis and S. schenckii, whilst little is known about the S. globosa cell wall and the immune response that its components trigger. Therefore, in this st… Show more
“…However, some variations were observed in the case of S. brasiliensis conidia, where the essential receptors are dectin-1 and TLR2, a result that could be related to the cell wall organization of this morphology ( Figure 10 ). 26 , 76 Figure 10 Phagocytosis and receptors involved in the immune recognition of different species of the Sporothrix pathogenic clade. Macrophages and dendritic cells can phagocytose yeast-like cells and conidia of S. schenckii, S. brasiliensis , and S. globosa.…”
Background
Sporotrichosis is a mycosis frequently caused by
Sporothrix schenckii, Sporothrix brasiliensis
, and
Sporothrix globosa
. The cell wall is a species-specific fungal structure with a direct role in activating the host’s immune response. The current knowledge about anti-
Sporothrix
immunity comes from studies using
S. schenckii
or
S. brasiliensis
and murine cells. Macrophages and dendritic cells detect and eliminate pathogens, and although the function of these cells links innate with adaptive immunity, little is known about their interaction with
Sporothrix
spp.
Methods
S. schenckii, S. brasiliensis
, and
S. globosa
conidia or yeast-like cells were co-incubated with human monocyte-derived macrophages or dendritic cells, and the phagocytosis and cytokine stimulation were assessed. These interactions were also performed in the presence of specific blocking agents of immune receptors or fungal cells with altered walls to analyze the contribution of these molecules to the immune cell-fungus interaction.
Results
Both types of immune cells phagocytosed
S. globosa
conidia and yeast-like cells to a greater extent, followed by
S. brasiliensis
and
S. schenckii
. Furthermore, when the wall internal components were exposed, the phagocytosis level increased for
S. schenckii
and
S. brasiliensis
, in contrast to
S. globosa
. Thus, the cell wall components have different functions during the interaction with macrophages and dendritic cells.
S. globosa
stimulated an increased proinflammatory response when compared to the other species. In macrophages, this was a dectin-1-, mannose receptor-, and TLR2-dependent response, but dectin-1- and TLR2-dependent stimulation in dendritic cells. For
S. schenckii
and
S. brasiliensis
, cytokine production was dependent on the activation of TLR4, CR3, and DC-SIGN.
Conclusion
The results of this study indicate that these species are recognized by immune cells differently and that this may depend on both the structure and cell wall organization of the different morphologies.
“…However, some variations were observed in the case of S. brasiliensis conidia, where the essential receptors are dectin-1 and TLR2, a result that could be related to the cell wall organization of this morphology ( Figure 10 ). 26 , 76 Figure 10 Phagocytosis and receptors involved in the immune recognition of different species of the Sporothrix pathogenic clade. Macrophages and dendritic cells can phagocytose yeast-like cells and conidia of S. schenckii, S. brasiliensis , and S. globosa.…”
Background
Sporotrichosis is a mycosis frequently caused by
Sporothrix schenckii, Sporothrix brasiliensis
, and
Sporothrix globosa
. The cell wall is a species-specific fungal structure with a direct role in activating the host’s immune response. The current knowledge about anti-
Sporothrix
immunity comes from studies using
S. schenckii
or
S. brasiliensis
and murine cells. Macrophages and dendritic cells detect and eliminate pathogens, and although the function of these cells links innate with adaptive immunity, little is known about their interaction with
Sporothrix
spp.
Methods
S. schenckii, S. brasiliensis
, and
S. globosa
conidia or yeast-like cells were co-incubated with human monocyte-derived macrophages or dendritic cells, and the phagocytosis and cytokine stimulation were assessed. These interactions were also performed in the presence of specific blocking agents of immune receptors or fungal cells with altered walls to analyze the contribution of these molecules to the immune cell-fungus interaction.
Results
Both types of immune cells phagocytosed
S. globosa
conidia and yeast-like cells to a greater extent, followed by
S. brasiliensis
and
S. schenckii
. Furthermore, when the wall internal components were exposed, the phagocytosis level increased for
S. schenckii
and
S. brasiliensis
, in contrast to
S. globosa
. Thus, the cell wall components have different functions during the interaction with macrophages and dendritic cells.
S. globosa
stimulated an increased proinflammatory response when compared to the other species. In macrophages, this was a dectin-1-, mannose receptor-, and TLR2-dependent response, but dectin-1- and TLR2-dependent stimulation in dendritic cells. For
S. schenckii
and
S. brasiliensis
, cytokine production was dependent on the activation of TLR4, CR3, and DC-SIGN.
Conclusion
The results of this study indicate that these species are recognized by immune cells differently and that this may depend on both the structure and cell wall organization of the different morphologies.
“…Next, we assessed the contribution of some pattern recognition receptors (PRRs) during the Sporothrix-PBMC interaction. We blocked dectin-1 with the antagonist laminarin [27] while blocking MR, CR3, TLR2, and TLR4 with monoclonal specific blocking antibodies [53,54]. The TNFα and IL-6 stimulation by the WT control strain was significantly affected by preincubation of human PBMCs with laminarin and anti-TLR2 and to a lesser extent by anti-TLR4 (Figure 5).…”
Section: The Gp70 Silencing Affected the Human Innate Immune Cell-spo...mentioning
Sporothrix schenckii is one of the etiological agents of sporotrichosis, a cutaneous and subcutaneous infection distributed worldwide. Like other medically relevant fungi, its cell wall is a molecular scaffold to display virulence factors, such as protective pigments, hydrolytic enzymes, and adhesins. Cell wall proteins with adhesive properties have been previously reported, but only a handful of them have been identified and characterized. One of them is Gp70, an abundant cell wall protein mainly found on the surface of yeast-like cells. Since the protein also has a role in the activity of 3-carboxy-cis,cis-muconate cyclase and its abundance is low in highly virulent strains, its role in the Sporothrix–host interaction remains unclear. Here, a set of GP70-silenced strains was generated, and the molecular and phenotypical characterization was performed. The results showed that mutants with high silencing levels showed a significant reduction in the adhesion to laminin and fibrinogen, enzyme activity, and defects in the cell wall composition, which included reduced mannose, rhamnose, and protein content, accompanied by an increment in β-1,3-glucans levels. The cell wall N-linked glycan content was significantly reduced. These strains induced poor TNFα and IL-6 levels when interacting with human peripheral blood mononuclear cells in a dectin-1-, TLR2-, and TLR4-dependent stimulation. The IL-1β and IL-10 levels were significantly higher and were stimulated via dectin-1. Phagocytosis and stimulation of neutrophil extracellular traps by human granulocytes were increased in highly GP70-silenced strains. Furthermore, these mutants showed virulence attenuation in the invertebrate model Galleria mellonella. Our results demonstrate that Gp70 is a versatile protein with adhesin properties, is responsible for the activity of 3-carboxy-cis,cis-muconate cyclase, and is relevant for the S. schenckii–host interaction.
“…Recently, the CW composition was analyzed in conidia, germlings, and yeast-like cells of S. globosa and compared with S. schenckii and S. brasiliensis . It was found that both conidia and yeast-like cells of S. globosa had a higher amount of chitin in their CWs, and all morphologies had more exposed β1,3-glucan on their surface compared to S. schenckii and S. brasiliensis [ 57 ]. The composition and structure of the fungal cell wall are influenced not only by environmental conditions but also by the cell cycle, changes in growth form, and other processes [ 58 , 59 , 60 , 61 ].…”
Glycoside hydrolases (GHs) are enzymes that participate in many biological processes of fungi and other organisms by hydrolyzing glycosidic linkages in glycosides. They play fundamental roles in the degradation of carbohydrates and the assembly of glycoproteins and are important subjects of studies in molecular biology and biochemistry. Based on amino acid sequence similarities and 3-dimensional structures in the carbohydrate-active enzyme (CAZy), they have been classified in 171 families. Members of some of these families also exhibit the activity of trans-glycosydase or glycosyl transferase (GT), i.e., they create a new glycosidic bond in a substrate instead of breaking it. Fungal glycosidases are important for virulence by aiding tissue adhesion and colonization, nutrition, immune evasion, biofilm formation, toxin release, and antibiotic resistance. Here, we review fungal glycosidases with a particular emphasis on Sporothrix species and C. albicans, two well-recognized human pathogens. Covered issues include a brief account of Sporothrix, sporotrichosis, the different types of glycosidases, their substrates, and mechanism of action, recent advances in their identification and characterization, their potential biotechnological applications, and the limitations and challenges of their study given the rather poor available information.
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