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Published on: May 18, 2016
Differential Recognition of Clinically Relevant Sporothrix Species by Human Mononuclear Cells
Laura C García-Carnero1, Iván Martínez-Duncker2, Manuela Gómez-Gaviria1
1Departamento de Biología, División de Ciencias Naturales y Exactas, Campus Guanajuato, Universidad de Guanajuato, Noria Alta s/n, col. Noria Alta, C.P., Guanajuato 36050, Gto., Mexico.
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 study, we aimed to analyze the cell wall composition of S. globosa in three morphologies (germlings, conidia, and yeast-like cells) and the differences in cytokine production when human peripheral blood mononuclear cells (PBMCs) interact with these morphotypes, using S. schenckii and S. brasiliensis as a comparison. We found that S. globosa conidia and yeast-like cells have a higher cell wall chitin content, while all three morphologies have a higher β-1,3-glucan content, which was found most exposed at the cell surface when compared to S. schenckii and S. brasiliensis. In addition, S. globosa has lower levels of mannose- and rhamnose-based glycoconjugates, as well as of N- and O-linked glycans, indicating that this fungal cell wall has species-specific proportions and organization of its components. When interacting with PBMCs, S. brasiliensis and S. globosa showed a similar cytokine stimulation profile, but with a higher stimulation of IL-10 by S. globosa. Additionally, when the inner cell wall components of S. globosa were exposed at the surface or N- and O-glycans were removed, the cytokine production profile of this species in its three morphotypes did not significantly change, contrasting with the S. schenckii and S. brasiliensis species that showed different cytokine profiles depending on the treatment applied to the walls. In addition, it was found that the anti-inflammatory response stimulated by S. globosa was dependent on the activation of dectin-1, mannose receptor, and TLR2, but not TLR4. All of these results indicate that the cell wall composition and structure of the three Sporothrix species in the three morphologies are different, affecting their interaction with human PBMCs and generating species-specific cytokine profiles.
Insights
This study reveals distinct cell wall compositions in Sporothrix species, influencing immune responses. Sporothrix globosa exhibits unique chitin and beta-glucan content, leading to species-specific cytokine production in human cells.
Area of Science:
- Mycology
- Immunology
- Fungal Pathogenesis
Background:
- Sporotrichosis is a global fungal infection caused by Sporothrix species.
- Limited knowledge exists regarding Sporothrix globosa's cell wall and immune interactions compared to S. schenckii and S. brasiliensis.
Purpose of the Study:
- To analyze the cell wall composition of S. globosa across different morphologies.
- To compare cytokine production triggered by S. globosa morphotypes interacting with human peripheral blood mononuclear cells (PBMCs).
- To contrast these findings with S. schenckii and S. brasiliensis.
Main Methods:
- Comparative analysis of S. globosa, S. schenckii, and S. brasiliensis cell wall composition (chitin, beta-glucan, glycoconjugates).
- Incubation of human PBMCs with different Sporothrix morphotypes.
- Measurement of cytokine production (e.g., IL-10) and assessment of immune receptor involvement (dectin-1, TLR2).
Main Results:
- S. globosa cell walls show higher chitin and exposed beta-1,3-glucan content.
- S. globosa elicits a distinct cytokine profile, including higher IL-10 stimulation, compared to other species.
- Immune response to S. globosa is less dependent on cell wall structural modifications than S. schenckii and S. brasiliensis.
Conclusions:
- Sporothrix species possess unique cell wall structures that dictate species-specific interactions with human immune cells.
- S. globosa's cell wall composition influences its immunomodulatory properties, promoting an anti-inflammatory response via dectin-1, mannose receptor, and TLR2.
- Understanding these differences is crucial for comprehending sporotrichosis pathogenesis and host-pathogen interactions.
