# Intersections between proteostasis and immunity: insights from Caenorhabditis elegans

## TL;DR

This review explores how protein homeostasis and immune responses interact in the nematode C. elegans, revealing conserved mechanisms relevant to human health.

## Contribution

The paper highlights conserved connections between proteostasis and immunity in C. elegans and their relevance to mammals.

## Key findings

- Pathogens interfere with host proteostasis to survive, while hosts detect these changes and mount immune responses.
- Impairment of one proteostasis pathway in C. elegans can lead to compensatory activation of another, benefiting the host.
- Proteostasis-immunity interactions in C. elegans are conserved in mammals, suggesting broader biological relevance.

## Abstract

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.

Summary: Discoveries from the nematode C. elegans have provided insight into the many connections between immune responses and proteostasis, with examples of conservation across species.