Emerging Role for the PERK/eIF2α/ATF4 in Human Cutaneous Leishmaniasis.

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State: Public
Version: Final published version
Serval ID
serval:BIB_E02D5E2D0E4B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Emerging Role for the PERK/eIF2α/ATF4 in Human Cutaneous Leishmaniasis.
Journal
Scientific reports
Author(s)
Dias-Teixeira K.L., Calegari-Silva T.C., Medina J.M., Vivarini Á.C., Cavalcanti Á., Teteo N., Santana AKM, Real F., Gomes C.M., Pereira RMS, Fasel N., Silva J.S., Aktas B.H., Lopes U.G.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Publication state
Published
Issued date
06/12/2017
Peer-reviewed
Oui
Volume
7
Number
1
Pages
17074
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
Leishmania parasites utilize adaptive evasion mechanisms in infected macrophages to overcome host defenses and proliferate. We report here that the PERK/eIF2α/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/eIF2α/ATF-4 pathway in cultured macrophages and infected human tissue and that this pathway is important for parasite survival and progression of the infection.
Keywords
Activating Transcription Factor 4/antagonists & inhibitors, Activating Transcription Factor 4/genetics, Activating Transcription Factor 4/metabolism, Animals, Endoplasmic Reticulum Stress, Eukaryotic Initiation Factor-2/metabolism, HEK293 Cells, Heme Oxygenase-1/genetics, Heme Oxygenase-1/metabolism, Humans, Leishmania/pathogenicity, Leishmaniasis, Cutaneous/metabolism, Leishmaniasis, Cutaneous/pathology, Macrophages/cytology, Macrophages/metabolism, Macrophages/parasitology, Mice, Mice, Inbred C57BL, NF-E2-Related Factor 2/genetics, NF-E2-Related Factor 2/metabolism, Nitric Oxide/metabolism, Phosphorylation, RAW 264.7 Cells, RNA Interference, RNA, Small Interfering/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
14/12/2017 19:12
Last modification date
20/08/2019 17:04
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