Abstract
Sporothrix schenckii sensu stricto and S. brasiliensis are usually associated to sporotrichosis, a subcutaneous mycosis worldwide distributed. Comparative analyses between these two species indicate they contain genetic and physiological differences that are likely to impact the interaction with host cells. Here, we study the composition of the cell wall from conidia, yeast-like cells and germlings of both species and found they contained the same sugar composition. The carbohydrate proportion in the S. schenckii sensu stricto wall was similar across the three cell morphologies, with exception in the chitin content, which was significantly different in the three morphologies. The cell wall from germlings showed lower rhamnose content and higher glucose levels than other cell morphologies. In S. brasiliensis, the wall sugars were constant in the three morphologies, but glucose was lower in yeast-like cells. In S. schenckii sensu stricto cells most of chitin and β1,3-glucan were underneath wall components, but in S. brasiliensis germlings, chitin was exposed at the cell surface, and β1,3-glucan was found in the outer part of the conidia wall. We also compared the ability of these cells to stimulate cytokine production by human peripheral blood mononuclear cells. The three S. schenckii sensu stricto morphologies stimulated increased levels of pro-inflammatory cytokines, when compared to S. brasiliensis cells; while the latter, with exception of conidia, stimulated higher IL-10 levels. Dectin-1 was a key receptor for cytokine production during stimulation with the three morphologies of S. schenckii sensu stricto, but dispensable for cytokine production stimulated by S. brasiliensis germlings. TLR2 and TLR4 were also involved in the sensing of Sporothrix cells, with a major role for the former during cytokine stimulation. Mannose receptor had a minor contribution during cytokine stimulation by S. schenckii sensu stricto yeast-like cells and germlings, but S. schenckii sensu stricto conidia and S. brasiliensis yeast-like cells stimulated pro-inflammatory cytokines via this receptor. In conclusion, S. brasiliensis and S. schenckii sensu stricto, have similar wall composition, which undergoes changes depending on the cell morphology. These differences in the cell wall composition, are likely to influence the contribution of immune receptors during cytokine stimulation by human monocytes.
Highlights
Fungal infections are a significant burden to both healthy and hospitalized populations, representing about 15% of hospitalacquired infections (Brown et al, 2012)
When a similar approach was used to determine the exposure of β1,3-glucan on the surface of the three morphologies of these Sporothrix species, we found that HK yeast-like cells and germlings from S. schenckii sensu stricto and S. brasiliensis displayed more labeling of this cell wall polysaccharide than the live cells, suggesting that most of the β1,3-glucan is naturally masked by components from the outer layer of the wall (Figure 1B)
When the same strategy was used to analyze the sensing of S. schenckii sensu stricto yeast-like cells by human peripheral blood mononuclear cells (PBMCs), we found that laminarin negatively influenced the stimulation of TNFα, interleukin 1β (IL-1β), interleukin 6 (IL-6), and interleukin 10 (IL-10) when live, HK or β-eliminated yeast-like cells were used in the interaction assays, suggesting a key role for dectin-1 in the sensing of this S. schenckii sensu stricto cell morphology (Figure 4)
Summary
Fungal infections are a significant burden to both healthy and hospitalized populations, representing about 15% of hospitalacquired infections (Brown et al, 2012). Sporothrix schenckii sensu lato is a cosmopolitan and dimorphic fungal pathogen, and the causative agent of human and animal sporotrichosis, an infection transmitted by contact of the subcutaneous tissue with contaminated material or infected animals (Mora-Montes et al, 2015; Zhang et al, 2015; Rodrigues et al, 2016). This fungal disease is worldwide distributed, and a significant number of cases have been reported in North and South America, Asia, some African countries and Australia (Chakrabarti et al, 2015). S. schenckii sensu stricto and S. brasiliensis are the most common species associated to human and animal sporotrichosis, respectively (Chakrabarti et al, 2015; Mora-Montes et al, 2015)
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