Molecular Insights into Cell-Mediated Immunity in Atypical Non-Ulcerated Cutaneous Leishmaniasis

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Batista, Luis Fabio S. ; Pacheco, Carmen M. Sandoval ; Flores, Gabriela V. Araujo ; Ferreira, Frederico M. ; Goncalves, Andre N. A. ; Sosa-Ochoa, Wilfredo H. ; da Matta, Vania L. R. ; Gomes, Claudia M. C. ; Zuniga, Concepcion ; Corbett, Carlos E. P. ; Jeffares, Daniel C. ; Nakaya, Helder I. ; Silveira, Fernando T. ; Laurenti, Marcia D.

• Tipo de documento: Artigo Científico
• Fonte: MICROORGANISMS; v. 13, n. 2, p. 20-pg., 2025-02-01.

Resumo

Leishmania (Leishmania) infantum chagasi infections range from asymptomatic (AS) to severe visceral leishmaniasis (VL). One of the manifestations is an atypical non-ulcerated cutaneous leishmaniasis (NUCL), which occurs in some locations of Central America with few cases of VL. We conducted a transcriptomic analysis of cell-mediated immunity (CMI) on blood samples from NUCL, AS, VL patients from Amapala, Honduras, and healthy controls. RNA-seq revealed a similar perturbation of gene expression in NUCL and AS. Eight gene signatures of CMI were found in NUCL involved in CD8+ T lymphocyte infiltration, reactive oxygen species generation, PD-1 receptor ligand, inflammasome assembly, chemotaxis, complement receptor and suppressor immune cell infiltration. NUCL was distinguished from VL by its up-regulation of differently expressed genes (DEGs) related to T lymphocyte exhaustion, adhesion and transmigration of leukocytes, and down-regulation of oxidative stress genes. In contrast, VL exhibited up-regulated DEGs involved in antigen cross-presentation, and similar to VL from Brazil, down-regulated DEGs involved in innate immunity. Corroborating the transcriptome findings, both the Leishmanin skin test, and the immunopathology of NUCL skin lesion defined NUCL as a proinflammatory condition, intermediate between the AS and VL clinical outcomes. That condition may be the underlying element for the benign nature of the NUCL. (AU)

• Processo FAPESP: 14/50315-0 - Leishmanioses na América Latina: uma perspectiva avançada sobre fatores imunopatogenéticos da infecção cutânea e visceral, imunomoduladores da saliva de vetores flebotomíneos e exo-antígenos imunogênicos de Leishmania (L.) infantum chagasi candidatos à vacina
• Beneficiário: Marcia Dalastra Laurenti
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 20/10430-6 - Abordagens genômicas para explorar as consequências da interação de genótipos biologicamente distintos de Leishmania infantum com hospedeiros vertebrados e o impacto na epidemiologia da Leishmaniose Visceral Americana
• Beneficiário: Luís Fábio da Silva Batista
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 22/16578-0 - Abordagem bilateral para estimar a base genética do parasito e do cão doméstico na expressão da resposta contra a infecção por Leishmania infantum: da base genética ao impacto epidemiológico
• Beneficiário: Luís Fábio da Silva Batista
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado