Emerging Role for the PERK/eIF2α/ATF4 in Human Cutaneous Leishmaniasis. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Dias-Teixeira, Karina; Calegari-Silva, Teresa; Medina, Jorge; Vivarini, Áislan; Cavalcanti, Átila; Teteo, Nataly; Santana, Alynne; Real, Fernando; Gomes, Ciro; Pereira, Renata; Fasel, Nicolas; Silva, João; Aktas, Bertal; Lopes, Ulisses
• Is Part Of: Scientific reports. Volume 7:Issue 1(2017)
• Page Start: 1
• Page End: 11
• Publication Date: 2017-12
• Subjects: Natural history -- Research -- Periodicals; Biology -- Research -- Periodicals; Physical sciences -- Research -- Periodicals; Earth sciences -- Research -- Periodicals; Environmental sciences -- Research -- Periodicals; 502.85
• DOI: 10.1038/s41598-017-17252-x
• Languages: English
• ISSNs: 2045-2322

Abstract

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 byLeishmania and this pathway is important forLeishmania amazonensis infection. Knocking down PERK or ATF4 expression or inhibiting PERK kinase activity diminishedL .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 speciesL .(V .) braziliensis . Our data demonstrates thatLeishmania 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.