TLR4 Regulates the Proinflammatory Response and Myeloperoxidase Activity in Neutrophils During Interaction with...

Sporothrix schenckii is a pathogenic fungus that triggers innate immune responses. Toll-like receptors (TLRs), such as TLR4, upon recognizing microbial components (including fungal ones), activate inflammatory and immune responses in cells. Meanwhile, in neutrophils, myeloperoxidase (MPO) is involved in oxidative mechanisms with antimicrobial activity. In this context, the aim of this study was to evaluate the role of TLR4 in the neutrophil response to S. schenckii and its potential relationship with MPO. To achieve this, human neutrophils, untreated or pre-treated with an anti-TLR4 antibody, were exposed for two hours to baseline conditions, lipopolysaccharide (LPS) stimulation, or S. schenckii conidia. Subsequently, viability, phagocytosis, MPO activity, and protein expression (TLR4, MPO) were assessed via Western blot. Additionally, gene expression (TLR4, MPO, IL8, TNF, IL18, IL1B) was evaluated using RT-qPCR, and IL-8 levels were quantified by ELISA. The results showed that S. schenckii conidia increased TLR4 and MPO expression in neutrophils. TLR4 blockade tended to reduce phagocytosis and fungal viability nonsignificantly while increasing MPO expression, altering cytokine production (increasing IL8, IL18, and TNF, and decreasing LPS-induced IL1B). These findings suggest that TLR4-mediated fungal recognition may modulate inflammation, MPO secretion, and cytokine release to control infection, highlighting its potential as an immunotherapeutic target.