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

TL;DR

This study explores how inflammasomes contribute to different forms of American cutaneous leishmaniasis, revealing distinct immune patterns that could lead to better treatments.

Contribution

The study identifies distinct transcriptomic and immunopathological profiles of inflammasome components across clinical forms of ACL.

Findings

Inflammasome-related genes like NLRP3, AIM2, and IL-1β are highly expressed in mucocutaneous leishmaniasis.

Anergic diffuse cutaneous leishmaniasis shows increased NLRP12 and NLRC4 with reduced GSDMD.

Localized leishmaniasis exhibits transitional profiles, indicating a complex pathogenesis.

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-1β, 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.

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