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Reporter assays of cell extracts from RAW\u2010264.7 macrophages infected with\n                    <jats:italic>L. (L.) amazonensis<\/jats:italic>\n                    or HEK\u2010293T cells cotransfected with TLR2 and PKR promoter constructions were employed. Primary macrophages of TLR2\u2010knockout (KO) or IFNR\u2010KO mice were infected, and the levels of PKR, IFN\u20101, and superoxide dismutase 1 (SOD1) transcript levels were investigated and compared. Immunohistochemical analysis of human biopsy lesions was evaluated for IFN\u20101 and PKR\u2010positive cells.\n                    <jats:italic>Leishmania<\/jats:italic>\n                    infection increased the expression of PKR and IFN\u2010\u03b2 on induction of PKR\u2010promoter activity. The observed effects required the engagement of TLR2. TLR2\u2010KO macrophages expressed low IFN\u2010\u03b2 and PKR levels postinfection with a reduced parasite load. We also revealed the requirement of PKR signaling for\n                    <jats:italic>Leishmania\u2010<\/jats:italic>\n                    induced IFN\u20101 expression, responsible for sustaining PKR expression and enhancing infection. Moreover, during infection, SOD1 transcripts increased and were also enhanced when IFN\u20101 was added to the cultures. Remarkably, SOD1 expression was abrogated in infected, dominant\u2010negative PKR\u2010expressing cells. Finally, lesions of patients with anergic diffuse cutaneous leishmaniasis exhibited higher levels of PKR\/IFN\u20101\u2010expressing cells compared to those with single cutaneous leishmaniasis. In summary, we demonstrated the mechanisms and relevance of the IFN\u20101\/PKR axis in the\n                    <jats:italic>Leishmania<\/jats:italic>\n                    infection.\u2014De Carvalho Vivarini, A., Pereira, R. M. S., Dias Teixeira, K. L., Calegari\u2010Silva, 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 leishmaniasis: interferon\u2010dependent expression of double\u2010stranded RNA\u2010kinase (PKR)\n                    <jats:italic>via<\/jats:italic>\n                    TLR2.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    25, 4162\u20134173 (2011).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.11-185165","type":"journal-article","created":{"date-parts":[[2011,8,16]],"date-time":"2011-08-16T23:52:51Z","timestamp":1313538771000},"page":"4162-4173","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Human cutaneous leishmaniasis: interferon\u2010dependent expression of double\u2010stranded RNA\u2010dependent protein kinase (PKR)\n                    <i>via<\/i>\n                    TLR2"],"prefix":"10.1096","volume":"25","author":[{"given":"\u00c1islan","family":"de Carvalho Vivarini","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Parasitologia Molecular Instituto de Biof\u00edsica Carlos Chagas Filho, CCS  Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"de Meirelles Santos Pereira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Parasitologia Molecular Instituto de Biof\u00edsica Carlos Chagas Filho, CCS  Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina Luiza Dias","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Parasitologia Molecular Instituto de Biof\u00edsica Carlos Chagas Filho, CCS  Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa Cristina","family":"Calegari\u2010Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Parasitologia Molecular Instituto de Biof\u00edsica Carlos Chagas Filho, CCS  Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Bellio","sequence":"additional","affiliation":[{"name":"Instituto de Microbiologia Professor Paulo de G\u00f3es Universidade Federal do Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcia Dalastra","family":"Laurenti","sequence":"additional","affiliation":[{"name":"Departamento de Patologia Faculdade de Medicina, Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Eduardo Pereira","family":"Corbett","sequence":"additional","affiliation":[{"name":"Departamento de Patologia Faculdade de Medicina, Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e1udia Maria","family":"de Castro Gomes","sequence":"additional","affiliation":[{"name":"Departamento de Patologia Faculdade de Medicina, Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo Pedro","family":"Soares","sequence":"additional","affiliation":[{"name":"Centro de Pesquisas Ren\u00e9 Rachou Funda\u00e7\u00e3o Oswaldo Cruz, Minas Gerais  Belo Horizonte Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arist\u00f3bolo Mendes","family":"Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Genes Inflamat\u00f3rios Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais  Belo Horizonte Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando Tobias","family":"Silveira","sequence":"additional","affiliation":[{"name":"Instituto Evandro Chagas Laborat\u00f3rio de Leishmaniose, Minist\u00e9rio da Sa\u00fade  Bel\u00e9m 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