Interplay between proteostasis pathways and innate immune responses in Caenorhabditis elegans
Year: 2026
Type: article
Abstract: ABSTRACT Microbial pathogens frequently manipulate host protein homeostasis to undermine immunity by targeting protein synthesis, folding, trafficking, and degradation. Conversely, effective immune responses themselves impose substantial proteostatic demands, as the rapid production of antimicrobial effectors increases the burden on cellular quality-control systems. This bidirectional pressure has likely driven the evolution of surveillance mechanisms that sense disruptions in protein homeostasis as indicators of infection. Using Caenorhabditis elegans as a genetically tractable model, recent studies have revealed that perturbations in proteostasis across multiple cellular compartments, including the cytosol, endoplasmic reticulum (ER), mitochondria, proteasome, and extracellular space, are actively integrated with innate immune signaling. Stress-response pathways such as the heat shock response, translational regulation, and the unfolded protein responses of the ER and mitochondria function not only to restore proteome integrity but also to directly shape immune gene expression and pathogen resistance in a context-dependent manner. This review highlights proteostasis as an evolutionarily conserved immune surveillance system, linking cellular stress sensing to host defense and offering broader insights into the coupling of stress adaptation, immunity, and organismal health.
Source: Infection and Immunity
DOI: 10.1128/iai.00037-26
Authors: Annesha Ghosh, Jogender Singh
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W7155054693