Sporotrichosis is a deep mycosis caused by dimorphic species of the genus Sporothrix, with differences in pathogenicity between S. schenckii and S. brasiliensis species. Recently, it was discovered that the cell wall
peptidorhamnomannan (PRM) from S. brasiliensis has additional unknown
rhamnose residues. We hypothesize that the structural differences of Sporothrix spp PRMs impact the host's immune response and may explain the severity of
sporotrichosis caused by S. brasiliensis. We demonstrate that S. brasiliensis yeasts and its PRM (S.b PRM) induced a strong inflammatory response in human PBMCs, with high production of TNF-α,
IL-6 and IL-1β and induction of T-helper
cytokines IFN-γ,
IL-17 and
IL-22. In contrast, S. schenckii yeasts and its PRM induced higher concentrations of
interleukin-1 receptor antagonist (IL-1Ra), which resulted in low production of T-helper
cytokines such as
IL-17 and
IL-22. CR3 and
dectin-1 were required for
cytokine induction by both PRMs, while TLR2 and TLR4 were required for the response of S.s PRM and S.b PRM, respectively. IL-1β and IL-1α production induced by S. brasiliensis yeasts and S.b PRM were dependent on
inflammasome and caspase-1 activation. S. schenckii and S.s PRM were able to induce IL-1β independent of ROS. In conclusion, these findings improve our understanding of the pathogenesis of Sporothrix spp. by reporting differences of immunological responses induced by S. schenckii and S. brasiliensis. The study also opens the gateway for novel treatment strategies targeting local
inflammation and tissue destruction induced by S. brasiliensis
infection through
IL-1 inhibition.