Endoplasmic reticulum stress and unfolded protein response in infection by intracellular parasites

Abstract

Perturbations of the physiological status of the endoplasmic reticulum (ER) trigger a specific response known as the ER stress response or unfolded protein response (UPR). In mammalian cells, the UPR is mediated by three ER transmembrane proteins (IRE1, PERK and ATF6) which activate three signaling cascades to restore ER homeostasis. In recent years, a cross-talk between UPR, inflammatory and microbial sensing pathways has been elucidated. Pathogen infection can lead to UPR activation; moreover, several pathogens subvert the UPR to promote their survival and replication. While the UPR in viral and bacterial infection has been characterized, little is known about the role of UPR in intracellular parasite infection. Here, we review recent findings on UPR induction/modulation by intracellular parasites in host cells.

Lay abstract:

The endoplasmic reticulum (ER) has a central role in maintaining homeostasis and in the regulation of innate immune response. Perturbations in the ER (ER stress) lead to a signaling cascade termed unfolded protein response (UPR), aimed at restoring cell homeostasis. The UPR pathways are strictly connected with innate immunity and inflammation. In fact, many pathogens (mainly viruses and bacteria) are known to induce/modulate the UPR in the host cell. The UPR triggered by intracellular parasites is still poorly investigated. Its characterization could contribute to explain the mechanisms of pathogenicity and to identify targets for the development of new therapeutic approaches.