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Automated Separation of C. elegans Variably Colonized by a Bacterial Pathogen
Published on: March 21, 2014
Pathogen subversion of neuro-epidermal signaling impairs lysosomal function to disrupt collagen homeostasis in
Qian Li1,2, Yating Liu1, Hanyi Chen1
1School of Life Sciences, Center for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, Southwest United Graduate School, State Key Laboratory of Conservation and Utilization of Bio-resources in Yunnan, Yunnan University, Kunming, China.
Abstract:
The epidermis relies on collagen-rich extracellular matrices (ECMs) to maintain barrier integrity against pathogens. Lysosomes regulate cuticle collagen turnover, yet how neuronal signaling modulates epidermal lysosomal function and collagen organization during infection remains unclear. Using Pseudomonas aeruginosa PA14-Caenorhabditis elegans infection model, we demonstrate that pathogen-induced neuronal signaling disrupts epidermal lysosomal activity and collagen remodeling. PA14 infection triggers neurons to secrete NSIF-1 (Neuronal Secreted Immune Factor 1), which translocates to the epidermis and impairs lysosomal acidification, maturation, and degradation by suppressing the transcription factor ELT-3. This disruption leads to disorganized collagen structure, compromising cuticle integrity and host resistance. Genetic mutation of nsif-1 restores lysosomal function, enhances collagen density, and improves survival, while neuron-specific nsif-1 knockdown confirms its neuronal origin. Moreover, NSIF-1 inhibits ELT-3 nuclear localization, blocking its role in lysosomal-dependent ECM repair. Our study reveals a neuro-epidermal axis wherein pathogens exploit neuronal signals to disrupt lysosomal function and collagen homeostasis, identifying NSIF-1 and ELT-3 as potential targets to counteract infection-driven ECM dysregulation.
