title: Unveiling the Role of the Integrated Endoplasmic Reticulum Stress Response in Leishmania Infection - Future Perspectives.
abstract: The integrated endoplasmic reticulum stress response (IERSR) is an evolutionarily conserved adaptive mechanism that ensures endoplasmic reticulum (ER) homeostasis and cellular survival in the presence of stress including nutrient deprivation, hypoxia, and imbalance of Ca(+) homeostasis, toxins, and microbial infection. Three transmembrane proteins regulate integrated signaling pathways that comprise the IERSR, namely, IRE-1 that activates XBP-1, the pancreatic ER kinase (PERK) that phosphorylates the eukaryotic translation initiation factor 2 and transcription factor 6 (ATF6). The roles of IRE-1, PERK, and ATF4 in viral and some bacterial infections are well characterized. The role of IERSR in infections by intracellular parasites is still poorly understood, although one could anticipate that IERSR may play an important role on the host's cell response. Recently, our group reported the important aspects of XBP-1 activation in Leishmania amazonensis infection. It is, however, necessary to address the relevance of the other IERSR branches, together with the possible role of IERSR in infections by other Leishmania species, and furthermore, to pursue the possible implications in the pathogenesis and control of parasite replication in macrophages.
authors: Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro , Rio de Janeiro , Brazil.
authors: K L
authors: KL
authors: Dias-Teixeira
authors: Institute of Microbiology Paulo de Goes, Federal University of Rio de Janeiro , Rio de Janeiro , Brazil.
authors: R M
authors: RM
authors: Pereira
authors: Department of Biochemistry and Immunology, University of São Paulo , Ribeirão Preto , Brazil.
authors: J S
authors: JS
authors: Silva
authors: Department of Biochemistry, Faculty of Biology and Medicine, Center for Immunity and Infection Lausanne, University of Lausanne , Lausanne , Switzerland.
authors: N
authors: N
authors: Fasel
authors: Laboratory of Translation, Department of Hematology, Brigham and Women's Hospital, Harvard Medical School , Boston, MA , USA.
authors: B H
authors: BH
authors: Aktas
authors: Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro , Rio de Janeiro , Brazil.
authors: U G
authors: UG
authors: Lopes
keywords: ATF4; ER stress; IFN-1; Leishmania; PERK; XBP-1