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

American cutaneous leishmaniasis (ACL), caused by <i>Leishmania (Leishmania) amazonensis</i> and <i>L. (Viannia) braziliensis</i>, presents a wide spectrum of clinical and immunopathological manifestations, ranging from localized cutaneous leishmaniasis (LCL) to severe forms...

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Main Authors: Larissa dos Santos Alcântara, Marliane Batista Campos, Ana Carolina Stocco Lima, Alessandra Pontillo, Kamilla Batista da Silva Souza, Aurea Favero Ferreira, Cristina Pires Camargo, Sueli Mieko Oba-Shinjo, Márcia Dalastra Laurenti, Carlos Eduardo Pereira Corbett, Vania L. R. da Matta, Helder Nakaya, Fernando T. Silveira, Claudia Maria de Castro Gomes
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Microorganisms
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Online Access:https://www.mdpi.com/2076-2607/13/5/980
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author Larissa dos Santos Alcântara
Marliane Batista Campos
Ana Carolina Stocco Lima
Alessandra Pontillo
Kamilla Batista da Silva Souza
Aurea Favero Ferreira
Cristina Pires Camargo
Sueli Mieko Oba-Shinjo
Márcia Dalastra Laurenti
Carlos Eduardo Pereira Corbett
Vania L. R. da Matta
Helder Nakaya
Fernando T. Silveira
Claudia Maria de Castro Gomes
author_facet Larissa dos Santos Alcântara
Marliane Batista Campos
Ana Carolina Stocco Lima
Alessandra Pontillo
Kamilla Batista da Silva Souza
Aurea Favero Ferreira
Cristina Pires Camargo
Sueli Mieko Oba-Shinjo
Márcia Dalastra Laurenti
Carlos Eduardo Pereira Corbett
Vania L. R. da Matta
Helder Nakaya
Fernando T. Silveira
Claudia Maria de Castro Gomes
author_sort Larissa dos Santos Alcântara
collection DOAJ
description American cutaneous leishmaniasis (ACL), caused by <i>Leishmania (Leishmania) amazonensis</i> and <i>L. (Viannia) braziliensis</i>, 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 <i>NLRP3</i>, <i>AIM2</i>, <i>NLRP12</i>, <i>NLRC4</i>, <i>CASP1</i>, <i>CASP5</i>, <i>GSDMD</i>, and <i>IL1B</i> 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 <i>NLRP3</i>, <i>AIM2</i>, and <i>IL-1β</i>, indicating an intensified inflammatory environment. ADCL, the hyporeactive form, displayed increased <i>NLRP12</i> and <i>NLRC4</i> expression with reduced <i>GSDMD</i>. 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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spelling doaj-art-5231649b28d0489b927df4cd9b87fcf32025-08-20T03:48:02ZengMDPI AGMicroorganisms2076-26072025-04-0113598010.3390/microorganisms13050980Transcriptomic and Immunopathological Profiles of Inflammasomes in Different Clinical Forms of American Cutaneous LeishmaniasisLarissa dos Santos Alcântara0Marliane Batista Campos1Ana Carolina Stocco Lima2Alessandra Pontillo3Kamilla Batista da Silva Souza4Aurea Favero Ferreira5Cristina Pires Camargo6Sueli Mieko Oba-Shinjo7Márcia Dalastra Laurenti8Carlos Eduardo Pereira Corbett9Vania L. R. da Matta10Helder Nakaya11Fernando T. Silveira12Claudia Maria de Castro Gomes13Laboratorio de Patologia de Moléstias Infecciosas—LIM-50 Departamento de Patologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Sao Paolo 01246-903, SP, BrazilInstituto Evandro Chagas, Departamento de Parasitologia, Belém 70300-000, PA, BrazilInstituto Evandro Chagas, Departamento de Parasitologia, Belém 70300-000, PA, BrazilLaboratório de Imunogenética, Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Sao Paolo 05508-000, SP, BrazilLaboratório de Imunogenética, Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Sao Paolo 05508-000, SP, BrazilLaboratorio de Patologia de Moléstias Infecciosas—LIM-50 Departamento de Patologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Sao Paolo 01246-903, SP, BrazilLaboratorio de Microcirurgia—Cirurgia Plástica—LIM-04 Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Sao Paolo 01246-903, SP, BrazilLaboratório de Biologia Celular e Molecular—LIM-15 Departamento de Neurologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Sao Paolo 01246-903, SP, BrazilLaboratorio de Patologia de Moléstias Infecciosas—LIM-50 Departamento de Patologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Sao Paolo 01246-903, SP, BrazilLaboratorio de Patologia de Moléstias Infecciosas—LIM-50 Departamento de Patologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Sao Paolo 01246-903, SP, BrazilLaboratorio de Patologia de Moléstias Infecciosas—LIM-50 Departamento de Patologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Sao Paolo 01246-903, SP, BrazilDepartamento de Análises Clínicas e Toxicológicas, Faculdade de Ciencias Farmaceuticas, Universidade de São Paulo, Sao Paolo 05508-220, SP, BrazilInstituto Evandro Chagas, Departamento de Parasitologia, Belém 70300-000, PA, BrazilLaboratorio de Patologia de Moléstias Infecciosas—LIM-50 Departamento de Patologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Sao Paolo 01246-903, SP, BrazilAmerican cutaneous leishmaniasis (ACL), caused by <i>Leishmania (Leishmania) amazonensis</i> and <i>L. (Viannia) braziliensis</i>, 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 <i>NLRP3</i>, <i>AIM2</i>, <i>NLRP12</i>, <i>NLRC4</i>, <i>CASP1</i>, <i>CASP5</i>, <i>GSDMD</i>, and <i>IL1B</i> 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 <i>NLRP3</i>, <i>AIM2</i>, and <i>IL-1β</i>, indicating an intensified inflammatory environment. ADCL, the hyporeactive form, displayed increased <i>NLRP12</i> and <i>NLRC4</i> expression with reduced <i>GSDMD</i>. 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.https://www.mdpi.com/2076-2607/13/5/980american cutaneous leishmaniasisinflammasomestranscriptomicimmunopathological profiles<i>Leishmania (Leishmania) amazonensis</i><i>Leishmania (Viannia) braziliensis</i>
spellingShingle Larissa dos Santos Alcântara
Marliane Batista Campos
Ana Carolina Stocco Lima
Alessandra Pontillo
Kamilla Batista da Silva Souza
Aurea Favero Ferreira
Cristina Pires Camargo
Sueli Mieko Oba-Shinjo
Márcia Dalastra Laurenti
Carlos Eduardo Pereira Corbett
Vania L. R. da Matta
Helder Nakaya
Fernando T. Silveira
Claudia Maria de Castro Gomes
Transcriptomic and Immunopathological Profiles of Inflammasomes in Different Clinical Forms of American Cutaneous Leishmaniasis
Microorganisms
american cutaneous leishmaniasis
inflammasomes
transcriptomic
immunopathological profiles
<i>Leishmania (Leishmania) amazonensis</i>
<i>Leishmania (Viannia) braziliensis</i>
title Transcriptomic and Immunopathological Profiles of Inflammasomes in Different Clinical Forms of American Cutaneous Leishmaniasis
title_full Transcriptomic and Immunopathological Profiles of Inflammasomes in Different Clinical Forms of American Cutaneous Leishmaniasis
title_fullStr Transcriptomic and Immunopathological Profiles of Inflammasomes in Different Clinical Forms of American Cutaneous Leishmaniasis
title_full_unstemmed Transcriptomic and Immunopathological Profiles of Inflammasomes in Different Clinical Forms of American Cutaneous Leishmaniasis
title_short Transcriptomic and Immunopathological Profiles of Inflammasomes in Different Clinical Forms of American Cutaneous Leishmaniasis
title_sort transcriptomic and immunopathological profiles of inflammasomes in different clinical forms of american cutaneous leishmaniasis
topic american cutaneous leishmaniasis
inflammasomes
transcriptomic
immunopathological profiles
<i>Leishmania (Leishmania) amazonensis</i>
<i>Leishmania (Viannia) braziliensis</i>
url https://www.mdpi.com/2076-2607/13/5/980
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