Proteins Potentially Involved in Immune Evasion Strategies in Sporothrix brasiliensis Elucidated by Ultra-High-Resolution Mass Spectrometry

Abstract

Sporotrichosis is an important disease in Brazil that is caused by fungi of the genus Sporothrix and affects cats and humans. Our work investigated the proteins differentially expressed by S. brasiliensis in order to find out why this species is more virulent and pathogenic than S. schenckii. We verified a set of proteins that may be related to immune escape and that can explain the high virulence.

Sporothrix brasiliensis induces a more severe disease associated with sustained Th17 and regulatory T cells responses than Sporothrix schenckii sensu stricto in mice

“…These authors compared the ability of S. brasiliensis and S. schenckii sensu stricto cells to stimulate cytokine production in human peripheral blood mononuclear cells and observed that conidia and yeast of S. schenckii sensu stricto induced increased levels of proinflammatory cytokines, when compared to S. brasiliensis cells. The poor stimulation of the innate immune system by S. brasiliensis during early stages of infection can be explained, at least in part, by differences in the cell wall composition (Martínez-Alvarez et al, 2017;Lopes-Bezerra et al, 2018) and differentially expressed proteins that are potentially involved in immune evasion between these two species (Rossato et al, 2018). These differences can impact the infiltration and activation of macrophages and possibly dendritic cells, favoring the higher and longer lasting systemic dissemination of S. brasiliensis when compared with S. schenckii sensu stricto.…”

“…Recently, it was reported that differences in the cell wall composition between S. schenckii sensu stricto and S. brasiliensis influence the contribution of immune receptors during cytokine stimulation by human mononuclear cells (Martínez-Alvarez et al, 2017). Other recent studies showed that several proteins potentially involved in immune evasion strategies are expressed in S. brasiliensis but not in S. schenckii (Rossato et al, 2018), and that S. brasiliensis produces the highest levels of oxidative stress in a murine model among the species of S. schenckii sensu lato (Mario et al, 2017). These findings suggest that there must also be differences in the stimulation of specific T cell responses between these two species.…”

Immunity and Treatment of Sporotrichosis

“…The virulence factors related to the Sporothrix schenckii complex are probably related to the clinical manifestations of the mycosis, but are not well known. Some of the reported molecules and mechanisms that act as virulence factors are glycoproteins, secreted proteins, extracellular vesicles, melanin, ergosterol peroxide, and the dimorphism of the fungus [ 16 , 24 , 25 , 26 , 27 ].…”

“…Several vesicle-associated proteins have been reported in Sporothrix . Extracellular cell wall glucanase is a protein transported by vesicles that contributes to the fungal virulence by inducing macrophages and other host cells lysis due to the remodeling of their surface [ 25 ]. Superoxide dismutase (SOD), another cell wall protein, contributes to the growth and survival of the pathogen under conditions of oxidative stress, just like inside macrophages, and its presence has been reported in Sporothrix [ 26 ].…”

“…All of the factors mentioned earlier are required for Sporothrix virulence and are also used for evasion of the host immune system. The knowledge of these virulence factors opens the possibility of understanding the differences in the virulence that exists between the Sporothrix species, as is the case for 9 out of 60 proteins differentially expressed in S. brasiliensis with respect to S. schenckii : aminopeptidase I, extracellular cell wall glucanase, Mn-superoxide dismutase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), heat shock 70-kDa protein 1/8, hydroxymethyl-glutaryl-coenzyme A (HMG-CoA) lyase, acetyl-CoA hydrolase, progesterone binding protein, and rhamnolipid biosynthesis 3-oxoacyl-(acyl-carrier-protein) reductase, where all of these are involved in the evasion of the host immune system [ 25 ]. Others exoantigens such as secreted proteins of 46, 60, 90, and 110 kDa are commonly secreted by S. schenckii , S. brasiliensis , and S. globosa [ 34 ].…”