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Transcriptomic landscape of skin lesions in cutaneous leishmaniasis reveals a strong CD8+ T cell immunosenescence signature linked to immunopathology.
Fantecelle, Carlos Henrique; Covre, Luciana Polaco; Garcia de Moura, Renan; Guedes, Herbert Leonel de Matos; Amorim, Camila Farias; Scott, Phillip; Mosser, David; Falqueto, Aloisio; Akbar, Arne N; Gomes, Daniel Claudio Oliveira.
Afiliação
  • Fantecelle CH; Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo, Vitoria, Brazil.
  • Covre LP; Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo, Vitoria, Brazil.
  • Garcia de Moura R; Division of Medicine, University College London, London, UK.
  • Guedes HLM; Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo, Vitoria, Brazil.
  • Amorim CF; Instituto de Microbiologia Professor Paulo de Goes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
  • Scott P; Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil.
  • Mosser D; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Falqueto A; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Akbar AN; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, USA.
  • Gomes DCO; Departamento de Medicina Social, Universidade Federal do Espírito Santo, Vitoria, Brazil.
Immunology ; 164(4): 754-765, 2021 12.
Article em En | MEDLINE | ID: mdl-34432883
The severity of lesions that develop in patients infected by Leishmania braziliensis is mainly associated with a highly cytotoxic and inflammatory cutaneous environment. Recently, we demonstrated that senescent T and NK cells play a role in the establishment and maintenance of this tissue inflammation. Here, we extended those findings using transcriptomic analyses that demonstrate a strong co-induction of senescence and pro-inflammatory gene signatures in cutaneous leishmaniasis (CL) lesions. The senescence-associated signature was characterized by marked expression of key genes such as ATM, Sestrin 2, p16, p21 and p38. The cell type identification from deconvolution of bulk sequencing data showed that the senescence signature was linked with CD8+ effector memory and TEMRA subsets and also senescent NK cells. A key observation was that the senescence markers in the skin lesions are age-independent of patients and were correlated with lesion size. Moreover, a striking expression of the senescence-associated secretory phenotype (SASP), pro-inflammatory cytokine and chemokines genes was found within lesions that were most strongly associated with the senescent CD8 TEMRA subset. Collectively, our results confirm that there is a senescence transcriptomic signature in CL lesions and supports the hypothesis that lesional senescent cells have a major role in mediating immunopathology of the disease.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leishmania braziliensis / Leishmaniose Cutânea / Linfócitos T CD8-Positivos / Transcriptoma / Imunossenescência Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Immunology Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leishmania braziliensis / Leishmaniose Cutânea / Linfócitos T CD8-Positivos / Transcriptoma / Imunossenescência Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Immunology Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido