| Author | Vivarini, Aislan de Carvalho | |
| Author | Pereira, Renata de Meirelles Santos | |
| Author | Teixeira, Karina Luiza Dias | |
| Author | Calegari-Silva, Teresa Cristina | |
| Author | Bellio, Maria | |
| Author | Laurenti, Marcia Dalastra | |
| Author | Corbett, Carlos Eduardo Pereira | |
| Author | Gomes, Claudia Maria de Castro | |
| Author | Soares, Rodrigo Pedro Pinto | |
| Author | Silva, Aristobolo Mendes | |
| Author | Silveira, Fernando Tobias | |
| Author | Lopes, Ulisses Gazos | |
| Access date | 2023-07-20T17:01:16Z | |
| Available date | 2023-07-20T17:01:16Z | |
| Document date | 2011 | |
| Citation | VIVARINI, Aislan de Carvalho et al. Human cutaneous leishmaniasis: interferon-dependent expression of double-stranded RNA-dependent protein kinase (PKR) via TLR2. FASEB J., v. 25, n. 12, p. 416241-73, 2011. doi: 10.1096/fj.11-185165. | en_US |
| ISSN | 0892-6638 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/59696 | |
| Language | eng | en_US |
| Publisher | Federation of American Societies for Experimental Biology | en_US |
| Rights | restricted access | |
| Title | Human cutaneous leishmaniasis: interferon-dependent expression of double-stranded RNA-dependent protein kinase (PKR) via TLR2 | en_US |
| Type | Article | |
| DOI | 10.1096/fj.11-185165 | |
| Abstract | We investigated the type I interferon (IFN-1)/PKR axis in the outcome of the Leishmania (Leishmania) amazonensis infection, along with the underlying mechanisms that trigger and sustain this signaling pathway. Reporter assays of cell extracts from RAW-264.7 macrophages infected with L. (L.) amazonensis or HEK-293T cells cotransfected with TLR2 and PKR promoter constructions were employed. Primary macrophages of TLR2-knockout (KO) or IFNR-KO mice were infected, and the levels of PKR, IFN-1, and superoxide dismutase 1 (SOD1) transcript levels were investigated and compared. Immunohistochemical analysis of human biopsy lesions was evaluated for IFN-1 and PKR-positive cells. Leishmania infection increased the expression of PKR and IFN-beta on induction of PKR-promoter activity. The observed effects required the engagement of TLR2. TLR2-KO macrophages expressed low IFN-beta and PKR levels postinfection with a reduced parasite load. We also revealed the requirement of PKR signaling for Leishmania-induced IFN-1 expression, responsible for sustaining PKR expression and enhancing infection. Moreover, during infection, SOD1 transcripts increased and were also enhanced when IFN-1 was added to the cultures. Remarkably, SOD1 expression was abrogated in infected, dominant-negative PKR-expressing cells. Finally, lesions of patients with anergic diffuse cutaneous leishmaniasis exhibited higher levels of PKR/IFN1-expressing cells compared to those with single cutaneous leishmaniasis. In summary, we demonstrated the mechanisms and relevance of the IFN-1/PKR axis in the Leishmania infection.-De Carvalho Vivarini, A., Pereira, R. M. S., Dias Teixeira, K. L., Calegari-Silva, T. C., Bellio, M., Laurenti, M. D., Corbett, C. E. P., de Castro Gomes, C. M., Soares, R. P., Mendes Silva, A., Silveira, F. T., Lopes, U. G. Human cutaneous leish-maniasis: interferon-dependent expression of double-stranded RNA-kinase (PKR) via TLR2. FASEB J. 25, 4162-4173 (2011). www.fasebj.org | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratorio de Parasitologia Molecular. Rio deJaneiro, Brazil | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratorio de Parasitologia Molecular. Rio deJaneiro, Brazil | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratorio de Parasitologia Molecular. Rio de Janeiro, Brazil | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratorio de Parasitologia Molecular. Rio de Janeiro, Brazil | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Professor Paulo de Goes. Rio de Janeiro, RJ, Brazil | en_US |
| Affilliation | Universidade de Sao Paulo. Faculdade de Medicina. Departamento de Patologia. São Paulo, SP, Brazil | en_US |
| Affilliation | Universidade de Sao Paulo. Faculdade de Medicina. Departamento de Patologia. São Paulo, SP, Brazil | en_US |
| Affilliation | Universidade de Sao Paulo. Faculdade de Medicina. Departamento de Patologia. São Paulo, SP, Brazil | en_US |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brazil | en_US |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Laboratorio de Genes Inflamatorios. Belo Horizonte, MG, Brazil | en_US |
| Affilliation | Ministério da Saude. Instituto Evandro Chagas. Laboratorio de Leishmaniose. Ministerio da Saude. Belem, PA, Brazil | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratorio de Parasitologia Molecular. Rio de Janeiro, Brazil | en_US |
| Subject | interferon-1 | en_US |
| Subject | Toll-like receptor 2 | en_US |
| Subject | SOD1 | en_US |
| Embargo date | 2099-12-31 | |
