Transcriptomic and Immunopathological Profiles of Inflammasomes in Different Clinical Forms of American Cutaneous Leishmaniasis.

American cutaneous leishmaniasis (ACL), caused by and , presents a wide spectrum of clinical and immunopathological manifestations, ranging from localized cutaneous leishmaniasis (LCL) to severe forms like anergic diffuse cutaneous (ADCL) and mucocutaneous leishmaniasis (MCL). Despite evidence of the immune response's complexity, the role of inflammasomes in disease severity and parasite persistence remains unclear. We investigated the transcriptomic and immunopathological profiles of inflammasome components in patient lesions across the clinical spectrum. Genes such as , , , , , , , and and all evaluated proteins, showed higher expression in ACL compared to healthy controls. Distinct inflammasome activation patterns were observed: MCL, the hyperreactive form, showed elevated , , and , indicating an intensified inflammatory environment. ADCL, the hyporeactive form, displayed increased and expression with reduced . Localized forms showed transitional profiles, highlighting ACL's multifactorial pathogenesis. These findings advance our understanding of inflammasome mechanisms in ACL, identifying potential therapeutic targets to modulate inflammation and improve management.