Human serum factors impact the interaction of Sporothrix spp. with human macrophages

L. Lopes Bezerra

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Since the first description of sporotrichosis, in 1898, this disease was considered as a benign cutaneous mycosis attributed to a single etiological agent, Sporothrix schenckii. This paradigm has changed after the discovery of two new pathogenic cryptic species, Sporothrix brasiliensis and Sporothrix globosa. Interestingly, these emerging pathogens are related to a zoonosis and a sapronosis, respectively, with a particular geographic distribution. Felis silvestris catus (domestic cats) infections by S. schenckii and S. brasiliensis are reported in the literature but cat-transmitted sporotrichosis is, so far, related to S. brasiliensis. Moreover, sporotrichosis caused by S. brasiliensis is a severe deep infection in felines and, disseminated and extracutaneous infections in humans are also frequently reported. How distinct is the biology and pathogenicity of these species? Our group showed that S. brasiliensis clinical isolates are more virulent compared with S. schenckii clinical isolates, in a subcutaneuous murine model. A new cell wall model is being proposed, showing that Sporothrix spp. have a unique cell wall architecture. In comparison to S. schenckii, S. brasiliensis has a thicker cell wall that correlates with a 30% higher chitin content and, an outermost cell wall layer with longer fibrils that can reach up to 400 nm. This fibrillar outer layer is composed by a Con-A reactive glycopeptide, the peptido-rhamnomannan (PRM). Furthermore, these longer fibrils interconnect S. brasiliensis yeast cells which is in agreement with recent publications that suggest this fungus can form biofilms. The rhamnomannan structure is similar in both species but, the rhamnose content is 100% higher in S. brasiliensis yeast cells. This observation can be related to new PRM epitopes. Interestingly, distinct from other dimorphic fungi, Sporothrix spp do not express α-glucan on their surface, a polymer that can mask β-glucan and, in consequence, dectin-1 recognition. Dectin-1 has a minor role on Sporothrix recognition by human monocytes but this is not due to the presence of α-glucan. These important findings correlate with a distinct recognition pattern and cytokine secretion profile by human monocyte derived macrophages challenged with both species. Our recent data suggest that another receptor, apart from TLR2 or TLR4, is involved in the uptake of S. brasiliensis by human macrophages. This interaction is mediated by human serum factors as well as the macrophage response.


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20th Congress of the International Society for Human and Animal Mycology, Amsterdam, the Netherlands
    • ISHAM 20th (2018)