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

Some bacteria interact with the endoplasmic reticulum (ER) to generate intracellular compartments that promote bacterial replication. However, conditions of physiological stress in the ER elicit the unfolded protein response (UPR), which is a cytoprotective response that is also involved in innate immune sensing. Here, Celli and Tsolis discuss how bacteria and the ER interact, including how bacteria induce the UPR, how subversion of the UPR promotes bacterial proliferation and how the UPR participates in innate immune responses against intracellular bacteria. 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), which also invokes innate immune signalling in response to invading microorganisms. Although it has been known for some time that the UPR is modulated by various viruses, recent evidence indicates that it also has multiple roles during bacterial infections. In this Review, we describe how bacteria interact with the ER, including how bacteria induce the UPR, how subversion of the UPR promotes bacterial proliferation and how the UPR contributes to innate immune responses against invading bacteria.