Pathogen subversion of neuro-epidermal signaling impairs lysosomal function to disrupt collagen homeostasis in Caenorhabditis elegans
- 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
- 2School of Chemical Science and Technology, Key Laboratory of Medicinal Chemistry for Natural Resource - Ministry of Education, 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.
Pathogens exploit host signaling to evade immune responses, but how they alter neuro-epidermal communication to compromise epidermal integrity remains unclear. This study shows that Pseudomonas aeruginosa-PA14 infection in C. elegans induces secretion of the neuropeptide-like factor NSIF-1, impairing epidermal lysosomal function and cuticle collagen organization.
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BibTeX
@article{li2026pathogen,
title = {{Pathogen subversion of neuro-epidermal signaling impairs lysosomal function to disrupt collagen homeostasis in Caenorhabditis elegans}},
author = {Qian Li and Yating Liu and Hanyi Chen and Weilie Xiao and Bin Qi},
journal = {PLOS Biology},
year = {2026},
month = sep,
doi = {10.1371/journal.pbio.3004016},
url = {https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004016},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Pathogen subversion of neuro-epidermal signaling impairs lysosomal function to disrupt collagen homeostasis in Caenorhabditis elegans
AU - Qian Li
AU - Yating Liu
AU - Hanyi Chen
AU - Weilie Xiao
AU - Bin Qi
PY - 2026
DA - 2026/09/22
JO - PLOS Biology
DO - 10.1371/journal.pbio.3004016
UR - https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004016
AB - 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. Pathogens exploit host signaling to evade immune responses, but how they alter neuro-epidermal communication to compromise epidermal integrity remains unclear. This study shows that Pseudomonas aeruginosa-PA14 infection in C. elegans induces secretion of the neuropeptide-like factor NSIF-1, impairing epidermal lysosomal function and cuticle collagen organization.
SN - 1545-7885
ER -