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.
Highlights
The endoplasmic reticulum (ER) is a dynamic tubular network involved in different processes such as protein folding, lipid synthesis, and the biogenesis of autophagosomes and peroxisomes [1]
We showed that induction of ER stress favors Leishmania amazonensis infection in a TLR2-dependent manner, culminating in the formation of X-box binding protein 1 (XBP-1)
It is well known that the integrated endoplasmic reticulum stress response (IERSR) can modulate viral and bacterial infection, promoting the induction of cytokines, including IFN-1, which can be determinant to the outcome of several infections
Summary
The endoplasmic reticulum (ER) is a dynamic tubular network involved in different processes such as protein folding, lipid synthesis, and the biogenesis of autophagosomes and peroxisomes [1]. PERK phosphorylates eIF2α, which reduces overall protein synthesis while upregulating the expression of activating transcription factor 4 (ATF4), which drives the expression of genes that play a critical role in restoring cellular homeostasis, resistance to oxidative stress together with genes related to the autophagic pathway and the innate immunity response. Both XBP-1 and ATF4 can be activated by toll-like receptors (TLRs). Due to classical function of IERSR in viral infections, it is relevant to test the role of PERK/ATF4 in viral co-infection and Leishmania
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
