{
  "abstract": "Background: Trichinella spiralis is a zoonotic parasitic nematode capable of infecting humans and animals, causing trichinellosis. It poses a critical threat to human health, livestock industry and food safety. The muscle larva of T. spiralis is encased within a collagen capsule that is believed to protect it from host immunity. A strong macrophage-dominated inflammatory infiltrate accumulates around the capsule, yet how macrophages contribute to capsule formation remains unclear. Our objective was to investigate the effect of macrophage on collagen capsule formation. Methodology/Principal findings: The results of immunofluorescence showed that S100A4 ⁺ cells accumulated in T. spiralis-infected muscle, and were composed predominantly of CD206 ⁺ macrophages. These macrophages were positioned in direct contact with α-SMA+ myofibroblasts. Moreover, numerous cells positive for both CD206 (M2 macrophage canonical marker) and α‑smooth muscle actin (α-SMA, biomarker of myofibroblasts) were observed. Western blot analysis revealed that S100A4 expression was restricted chiefly to M2 macrophage and its expression was markedly amplified by IL-4 together with excretory–secretory (ES) products from muscle larvae of T. spiralis. qPCR showed that inhibiting S100a4 transcription reduced Arg1 mRNA levels in macrophages activated by ES and IL-4. Immunofluorescence and western blot analysis showed the activated macrophages induced modest upregulation of α-SMA in fibroblasts. Immunohistochemistry revealed that inhibition of S100A4 by niclosamide reduced the expressions of CD206, TGF-β1 and collagen I in T. spiralis-infected muscle. Compared with albendazole alone, the combination of niclosamide and albendazole further reduced the larval burden in T. spiralis-infected mice. Conclusions/Significance: In conclusion, infection with T. spiralis significantly upregulated S100A4 expression in skeletal muscle-infiltrating macrophages. S100A4 further promoted macrophage M2 polarization. The M2-like macrophages either drove fibroblast activation or acquired myofibroblast-like features, thereby fostering collagen capsule formation. Blocking S100A4 diminished macrophage M2 polarization, prevented collagen capsule formation, and represented a potential adjunctive strategy against trichinellosis. Author summary: It is well known that T. spiralis provokes a robust inflammatory response encircling the collagen capsule that houses the muscle larva in skeletal muscle. The role of inflammatory cells in collagen capsule formation is debated. In this study, we revealed that macrophages densely accumulated around the muscle larvae of T. spiralis. The muscle larvae increased skeletal muscle IL‑4 levels to drive the expression of S100A4 in macrophages. S100A4 further enhanced macrophage M2 polarization. M2-like macrophages induced fibroblast‑to‑myofibroblast transition by secreting S100A4 and TGF-β1, or directly converted into myofibroblast-like cells, which synthesized the extracellular matrix components (ECM) and thereby fostering collagen capsule formation. Inhibition of S100A4 by niclosamide robustly attenuated infection-triggered collagen deposition and concurrently enhanced the efficacy of albendazole against T. spiralis muscle larvae.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pathogen Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Meng Ying Gao"
    },
    {
      "name": "Chen Chen Dong"
    },
    {
      "name": "Yue Chun Tang"
    },
    {
      "name": "Ruo Qi Wang"
    },
    {
      "name": "Li Wang"
    },
    {
      "name": "You Jia Ge"
    },
    {
      "name": "Qiao Yu Geng"
    },
    {
      "name": "Peng Jiang"
    },
    {
      "name": "Zi Fang Zhang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ch5bbs7jm03a6.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pntd.0014647",
  "fulltext_url": "https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014647",
  "id": "ch5bbs7jm03a6",
  "issns": [
    "1935-2735"
  ],
  "landing_url": "https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014647",
  "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",
      "2725|Parasitic Diseases Research and Treatment"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Biological tissue/Connective tissue/Connective tissue cells/Fibroblasts"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Musculoskeletal system/Muscles/Skeletal muscles"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Respiratory system/Thoracic diaphragm"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Collagens"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Blood cells/White blood cells/Macrophages"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Connective tissue cells/Fibroblasts"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Immune cells/White blood cells/Macrophages"
    ],
    [
      "plos",
      "/Biology and life sciences/Developmental biology/Life cycles/Larvae"
    ],
    [
      "plos",
      "/Biology and life sciences/Immunology/Immune cells/White blood cells/Macrophages"
    ],
    [
      "plos",
      "/Biology and life sciences/Immunology/Immune response/Inflammation"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Biological tissue/Connective tissue/Connective tissue cells/Fibroblasts"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Musculoskeletal system/Muscles/Skeletal muscles"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Respiratory system/Thoracic diaphragm"
    ],
    [
      "plos",
      "/Medicine and health sciences/Clinical medicine/Signs and symptoms/Inflammation"
    ],
    [
      "plos",
      "/Medicine and health sciences/Immunology/Immune cells/White blood cells/Macrophages"
    ],
    [
      "plos",
      "/Medicine and health sciences/Immunology/Immune response/Inflammation"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pharmacology/Routes of administration/Intraperitoneal injections"
    ]
  ],
  "openalex": "W7213312243",
  "pdf_url": "https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0014647&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-15",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/ch5bbs7jm03a6.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:49Z",
      "native_id": "10.1371/journal.pntd.0014647",
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      "url": "https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014647"
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  "subjects": [
    {
      "field": "biology",
      "origin": "plos:cell biology",
      "subfield": "cell-biology"
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    {
      "field": "biology",
      "origin": "plos:immunology",
      "subfield": "immunology"
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    {
      "field": "medicine",
      "origin": "plos:anatomy",
      "subfield": "physiology"
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  ],
  "title": "S100A4 enhances the pro-fibrotic effect of macrophage to promote collagen capsule formation of Trichinella spiralis",
  "title_text": "S100A4 enhances the pro-fibrotic effect of macrophage to promote collagen capsule formation of Trichinella spiralis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:49Z",
  "url": "https://research.draconitic.com/paper/ch5bbs7jm03a6",
  "venue": "PLOS Neglected Tropical Diseases",
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}