{
  "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.\n\nPathogens 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.",
  "abstract_shown": true,
  "affiliations": [
    "School 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",
    "School of Chemical Science and Technology, Key Laboratory of Medicinal Chemistry for Natural Resource - Ministry of Education, Yunnan University, Kunming, China"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Qian Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Yating Liu"
    },
    {
      "name": "Hanyi Chen"
    },
    {
      "name": "Weilie Xiao"
    },
    {
      "name": "Bin Qi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6en47t24vp21p.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pbio.3004016",
  "fulltext_url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004016",
  "id": "6en47t24vp21p",
  "issns": [
    "1545-7885"
  ],
  "landing_url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004016",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2403|Invertebrate Immune Response Mechanisms"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Integumentary system/Skin/Epidermis"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Reproductive system/Genital anatomy/Gonads"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Collagens"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular structures and organelles/Lysosomes"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Neurons"
    ],
    [
      "plos",
      "/Biology and life sciences/Molecular biology/Molecular biology techniques/DNA construction/Plasmid construction"
    ],
    [
      "plos",
      "/Biology and life sciences/Neuroscience/Cellular neuroscience/Neurons"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Eukaryota/Animals/Invertebrates/Nematoda/Caenorhabditis/Caenorhabditis elegans"
    ],
    [
      "plos",
      "/Biology and life sciences/Zoology/Animals/Invertebrates/Nematoda/Caenorhabditis/Caenorhabditis elegans"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Integumentary system/Skin/Epidermis"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Reproductive system/Genital anatomy/Gonads"
    ],
    [
      "plos",
      "/Research and analysis methods/Animal studies/Experimental organism systems/Animal models/Caenorhabditis elegans"
    ],
    [
      "plos",
      "/Research and analysis methods/Animal studies/Experimental organism systems/Model organisms/Caenorhabditis elegans"
    ],
    [
      "plos",
      "/Research and analysis methods/Imaging techniques/Fluorescence imaging"
    ],
    [
      "plos",
      "/Research and analysis methods/Model organisms/Caenorhabditis elegans"
    ],
    [
      "plos",
      "/Research and analysis methods/Molecular biology techniques/DNA construction/Plasmid construction"
    ]
  ],
  "openalex": "W7214041768",
  "pdf_url": "https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3004016&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-22",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/6en47t24vp21p.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:43Z",
      "native_id": "10.1371/journal.pbio.3004016",
      "source": "plos",
      "url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004016"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "plos:cell biology",
      "subfield": "cell-biology"
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    {
      "field": "medicine",
      "origin": "plos:anatomy",
      "subfield": "physiology"
    }
  ],
  "title": "Pathogen subversion of neuro-epidermal signaling impairs lysosomal function to disrupt collagen homeostasis in Caenorhabditis elegans",
  "title_text": "Pathogen subversion of neuro-epidermal signaling impairs lysosomal function to disrupt collagen homeostasis in Caenorhabditis elegans",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:43Z",
  "url": "https://research.draconitic.com/paper/6en47t24vp21p",
  "venue": "PLOS Biology",
  "versions": []
}