Bacteria, the endoplasmic reticulum and the unfolded protein response: friends or foes?

The unfolded protein response (UPR) is a cytoprotective response that is aimed at restoring cellular homeostasis following physiological stress exerted on the endoplasmic reticulum (ER). The UPR is also invoked in innate immune signalling in response to invading microorganisms.Several intracellular bacterial pathogens exploit the host secretory pathway to generate replication-permissive vacuoles that are derived from, or that closely interact with, the ER. Their resulting proliferation in the ER can elicit the UPR.Intracellular bacteria can either induce or downregulate the UPR to promote their survival, possibly via the concerted action of various effector molecules.ER stress and innate immune signalling pathways intersect in the control of inflammatory responses to invading microorganisms. In this context, the UPR can directly detect bacterial toxins or effectors, or can sense and respond to cellular alterations that are caused by these pathogenic molecules, which leads to the activation of pro-inflammatory responses that provide protection against bacterial infections.Bacterial pathogens have evolved molecular mechanisms that mitigate or exploit the UPR to promote their intracellular survival and proliferation.