Intersections between proteostasis and immunity: insights from Caenorhabditis elegans

Cells must properly synthesize, fold and degrade proteins to maintain protein homeostasis, or proteostasis. Studies in the model nematode host Caenorhabditis elegans have illuminated different ways in which proteostasis intersects with immune responses against pathogen infection, which is the focus of this Review. For example, pathogens often interfere with host proteostasis pathways to survive and replicate. Hosts, in turn, can sense these perturbations and then trigger immune responses, creating additional burdens on proteostasis. This Review is organized by the cellular compartments in which proteostasis pathways are activated, starting with the cytosolic processes of protein synthesis, folding, degradation and the ubiquitin-proteasome system. Next, we cover autophagy and lysosome-related processes, followed by pathways triggered in the endoplasmic reticulum and mitochondria. We discuss infections in C. elegans by bacteria, viruses, microsporidia and oomycetes; all of these pathogen types infect humans. We provide examples of how findings in C. elegans relate to mammals, noting how the coordination of proteostasis and immunity can be conserved across species. We emphasize a recurring theme in C. elegans that impairment of one proteostasis pathway can lead to compensatory activation of another pathway, ultimately providing a health benefit to the host, highlighting organismal resilience.