Farnesol modulates seric and splenic purinergic signaling during disseminated sporotrichosis by <i>Sporothrix brasiliensis</i> : improvement of immune response

Sporotrichosis is an implantation mycosis induced by exposure to thermodimorphic fungi of genus Sporothrix, which affects both humans and animals, resulting in severe inflammatory responses. Purinergic signaling has been implicated in pathogenesis of fungal infections, recognized as a critical system for modulating immune responses and triggering effector mechanisms during sporotrichosis. Natural products have emerged as promising modulators of immune responses, particularly through their influence on purinergic signaling. Among these, farnesol, a sesquiterpene alcohol, demonstrated anti-inflammatory effects during sporotrichosis. However, the pathways involved in farnesol anti-inflammatory effects during S. brasiliensis infection remain to be determined. The aim of this study was to determine whether farnesol exerts a protective effect against S. brasiliensis-induced inflammatory damage via modulation of purinergic enzymes and purinergic molecules. Serum and splenic E-nucleoside triphosphate diphosphohydrolase (E-NTPDase) activity for adenosine triphosphate (ATP) was stimulated in infected rats compared to uninfected rats, while E-adenosine deaminase (E-ADA) activity was reduced. Serum and splenic extracellular levels of ATP and adenosine were elevated in infected rats compared to uninfected, as well as serum levels of interleukin 2 (IL-2) and interleukin-6 (IL-6). Farnesol diminished S. brasiliensis-initiated rise in serum and splenic E-NTPDase and elevation in levels of IL-2 and IL-6. In addition, farnesol blocked fungal-mediated fall in serum and splenic E-ADA activities and decreased alterations on extracellular levels of ATP and adenosine. Farnesol exerted protective effects involved stimulation of purinergic signaling enzyme activities and consequently regulation of purine metabolism, associated with elevated cytokine levels, thereby ameliorating immune response during sporotrichosis.