Sporotrichosis is an infection that is caused by the thermo-dimorphic fungus Sporothrix schenckii, characterized by the appearance of skin and subcutaneous lesions, with later disease of lymphatic vessels, lymph nodes and visceral organs. The immunological mechanisms involved in the prevention and control of this disease suggests that innate immunity and cell-mediated play an important role in protecting the host against S. schenckii. The innate immune system express pattern recognition receptors (PRRs - "Pattern-Recognition Receptor") that detect and respond to the presence of molecular patterns associated with pathogens (PAMPs - "Pathogen-Associated Molecular Patterns"). The receptors NLRs ("NOD-Like Receptor") are cytoplasmatic proteins present in phagocytes that act as secondary sensors. The antigen recognition allows the receiver NLRP3 is activated, thereby allowing the connecting with the adapter molecule ASC ("Apoptosis-associated protein containing a Speck-like Caspase recruitment domain"), that activates caspase-1, forming protein complexes called inflammasomes. The activation of inflammasome allows triggering the production of pro-inflammatory cytokines, it culminates in the maturation of pró-IL-1² and pró-IL-18 to the active forms, IL-1² and IL-18. In turn, these interleukins contribute to the host defense against infections by increasing the antimicrobial properties of phagocytes and initiate adaptive immune responses Th1 and Th17, establishing a connection between different immune mechanisms. Experimental evidences shows that inflammasome plays an important role in antifungal host defense, however there is no information available about his involvement in infections caused by S. Schenckii. Therefore, the main objective of this project is to investigate the role of inflammasome in experimental sporotrichosis and the mechanisms by which components contribute to the modulation of an immune response in infection by S. schenckii, therefore understand how this protein complex works is fundamental to the development of appropriate therapeutic strategies.
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