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

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Alcantara, Larissa dos Santos ; Campos, Marliane Batista ; Lima, Ana Carolina Stocco ; Pontillo, Alessandra ; Souza, Kamilla Batista da Silva ; Ferreira, Aurea Favero ; Camargo, Cristina Pires ; Oba-Shinjo, Sueli Mieko ; Laurenti, Marcia Dalastra ; Corbett, Carlos Eduardo Pereira ; da Matta, Vania L. R. ; Nakaya, Helder ; Silveira, Fernando T. ; Gomes, Claudia Maria de Castro

• Document type: Journal article
• Source: MICROORGANISMS; v. 13, n. 5, p. 15-pg., 2025-04-24.

Abstract

American cutaneous leishmaniasis (ACL), caused by Leishmania (Leishmania) amazonensis and L. (Viannia) braziliensis, 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 NLRP3, AIM2, NLRP12, NLRC4, CASP1, CASP5, GSDMD, and IL1B 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 NLRP3, AIM2, and IL-1 beta, indicating an intensified inflammatory environment. ADCL, the hyporeactive form, displayed increased NLRP12 and NLRC4 expression with reduced GSDMD. 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. (AU)

• FAPESP's process: 14/50315-0 - Leishmaniasis in Latin America: an advanced perspective on immunopathogenetic factors of cutaneous and visceral infection, immunomodulators of the sandflies vector saliva and immunogenic exo-antigens of Leishmania (L.) infantum chagasi as vaccine candidates
• Grantee: Marcia Dalastra Laurenti
• Support Opportunities: Research Projects - Thematic Grants