The impact of the absence of Toll-like receptor-2 during Sporothrix brasiliensis infection.

PURPOSE: Sporothrix brasiliensis, a member of the Sporothrix schenckii complex, is a major cause of epidemic outbreaks of sporotrichosis due to its greater virulence and ability to evade the immune system. The absence of studies about this species led to this study, with the aim to evaluate the importance of Toll-like receptor-2 (TLR-2) during S. brasiliensis infection.

METHODOLOGY: In vitro assays were performed using bone marrow-derived macrophages from both wild-type (C57BL/6) and TLR-2 knockout (-/-) mice. In vivo assays were also performed, on which the mice (C57BL/6 and TLR-2-/-) were intraperitoneally infected with S. brasiliensis yeast American Type Culture Collection MYA-4831 and euthanized on days 7, 14 and 28 post infection. The following parameters were then evaluated: fungal burden in spleen, liver, kidney and brain; the production of cytokines TNF-α, IFN-γ, IL-4, IL-2, IL-6 and IL-10.

RESULTS

The in vitro results showed that the absence of TLR-2 resulted in impaired phagocytosis, microbicide mechanisms utilizing the production of nitric oxide, and the cytokine production (TNF-α, IL-6 and IL-10). The in vivo results demonstrated that the absence of TLR-2 during experimental S. brasiliensis infection promoted increased dissemination after 14 and 28 days and suggests a polarized Th17 response in an attempt to control the infection.

CONCLUSIONS

TLR-2 signalling appears to be important in the innate immune response against S. brasiliensis.