Emerging Role for the PERK/eIF2 alpha/ATF4 in Human Cutaneous Leishmaniasis

dc.citation.volume7
dc.contributor.authorDias-Teixeira, Karina Luiza
dc.contributor.authorCalegari-Silva, Teresa C.
dc.contributor.authorMedina, Jorge M.
dc.contributor.authorVivarini, Aislan C.
dc.contributor.authorCavalcanti, Atila
dc.contributor.authorTeteo, Nataly
dc.contributor.authorSantana, Alynne Karen M.
dc.contributor.authorReal, Fernando [UNIFESP]
dc.contributor.authorGomes, Ciro M.
dc.contributor.authorSantos Pereira, Renata Meirelles
dc.contributor.authorFasel, Nicolas
dc.contributor.authorSilva, Joao S.
dc.contributor.authorAktas, Bertal H.
dc.contributor.authorLopes, Ulisses G.
dc.coverageLondon
dc.date.accessioned2020-07-02T18:52:20Z
dc.date.available2020-07-02T18:52:20Z
dc.date.issued2017
dc.description.abstractLeishmania parasites utilize adaptive evasion mechanisms in infected macrophages to overcome host defenses and proliferate. We report here that the PERK/eIF2 alpha/ATF4 signaling branch of the integrated endoplasmic reticulum stress response (IERSR) is activated by Leishmania and this pathway is important for Leishmania amazonensis infection. Knocking down PERK or ATF4 expression or inhibiting PERK kinase activity diminished L. amazonensis infection. Knocking down ATF4 decreased NRF2 expression and its nuclear translocation, reduced HO-1 expression and increased nitric oxide production. Meanwhile, the increased expression of ATF4 and HO-1 mRNAs were observed in lesions derived from patients infected with the prevalent related species L.(V.) braziliensis. Our data demonstrates that Leishmania parasites activate the PERK/eIF2 alpha/ATF-4 pathway in cultured macrophages and infected human tissue and that this pathway is important for parasite survival and progression of the infection.en
dc.description.affiliationUniv Fed Rio de Janeiro, Inst Biophys, Lab Mol Parasitol, BR-21949902 Rio De Janeiro, RJ, Brazil
dc.description.affiliationBrigham & Womens Hosp, Dept Med, Hematol Lab Translat, 75 Francis St, Boston, MA 02115 USA
dc.description.affiliationHarvard Med Sch, Boston, MA 02115 USA
dc.description.affiliationUniv Fed Rio de Janeiro, Inst Med Biochem, BR-21949902 Rio De Janeiro, RJ, Brazil
dc.description.affiliationUniv Sao Paulo, Dept Biochem & Immunol, BR-14049900 Ribeirao Preto, SP, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, BR-04023062 Sao Paulo, SP, Brazil
dc.description.affiliationUniv Brasilia, Fac Med, BR-70910900 Brasilia, DF, Brazil
dc.description.affiliationUniv Fed Rio de Janeiro, Inst Microbiol Paulo de Goes, BR-21942902 Rio De Janeiro, Brazil
dc.description.affiliationUniv Lausanne, Fac Biol & Med, Dept Biochem, Ctr Immun & Infect Lausanne, CH-1066 Epalinges, Switzerland
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, BR-04023062 Sao Paulo, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipCAPES [043/12]
dc.description.sponsorshipFAPERJ
dc.description.sponsorshipNCI [R01CA152312]
dc.description.sponsorshipFNRS [N.310030-173180]
dc.description.sponsorshipFNRS International Cooperation [IZRJZ3-164176/1]
dc.description.sponsorshipIDCAPES [043/12]
dc.description.sponsorshipIDFAPERJ
dc.description.sponsorshipIDNCI [R01CA152312]
dc.description.sponsorshipIDFNRS [N.310030-173180]
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.1038/s41598-017-17252-x
dc.identifier.citationScientific Reports. London, v. 7, p. -, 2017.
dc.identifier.doi10.1038/s41598-017-17252-x
dc.identifier.fileWOS000417135800013.pdf
dc.identifier.issn2045-2322
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/54008
dc.identifier.wosWOS:000417135800013
dc.language.isoeng
dc.publisherNature Publishing Group
dc.relation.ispartofScientific Reports
dc.rightsAcesso aberto
dc.titleEmerging Role for the PERK/eIF2 alpha/ATF4 in Human Cutaneous Leishmaniasisen
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