{
  "abstract": "Tripartite motif-containing 21 (TRIM21) is an E3 ubiquitin ligase that binds viral and host proteins to mediate antiviral defense. Its role in Mycobacterium tuberculosis (Mtb) infection, however, is unclear. Here, our analysis of human TB transcriptomic datasets showed that TRIM21 expression levels correlate with TB progression in human patients. We further demonstrated that TRIM21 deficiency suppresses Mtb growth in both macrophages and a murine model of tuberculosis (TB). Mechanistically, TRIM21 limits host resistance to Mtb through a non-canonical pathway distinct with its E3 ligase activity. It physically interacts with the RNA helicase DEAD-box helicase family member DDX3X and disrupts phase separation dynamics required for stress granule (SG) assembly. Impaired SG formation compromises innate immune responses, thereby facilitating intracellular bacterial growth and creating a permissive cellular environment for Mtb growth. Consistent with these genetic findings, pharmacological inhibition of TRIM21 restricted Mtb growth in experimental macrophage and murine models. Together, these findings uncover a non-canonical role of TRIM21 in Mtb infection and highlight its potential as a therapeutic target for host-directed therapy against TB. Author summary: Tuberculosis (TB) remains one of the world’s most serious infectious diseases, and better treatments are urgently needed to improve outcomes for patients. Because host immunity plays a critical role in controlling Mycobacterium tuberculosis (Mtb) infection, host-directed therapy (HDT), which enhances protective host responses, has emerged as a promising complementary approach.",
  "abstract_shown": true,
  "affiliations": [
    "Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, School of Medicine, Shenzhen University, Shenzhen, China",
    "Guangzhou Medical Research Institute of Infectious Diseases, Infectious Disease Center, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China",
    "Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Pharmacology and International Cancer Center, School of Medicine, Shenzhen, China"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ruiyao Xu"
    },
    {
      "affs": [
        1
      ],
      "name": "Mengru Lu"
    },
    {
      "affs": [
        2
      ],
      "name": "Gaoyan Wang"
    },
    {
      "name": "Ximeng Zhang"
    },
    {
      "name": "Yuxing Huang"
    },
    {
      "name": "Yu Wang"
    },
    {
      "name": "Qing Yu"
    },
    {
      "name": "Yaxuan Wang"
    },
    {
      "name": "Dan Chen"
    },
    {
      "name": "Yunlong Hu"
    },
    {
      "name": "Chenyan Shi"
    },
    {
      "name": "Yi Cai"
    },
    {
      "name": "Li Fu"
    },
    {
      "name": "Xinchun Chen"
    },
    {
      "name": "Youchao Dai"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6zb4416swc3hz.bib",
  "cited_by": 1,
  "doi": "10.1371/journal.ppat.1014553",
  "fulltext_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014553",
  "id": "6zb4416swc3hz",
  "issns": [
    "1553-7374"
  ],
  "landing_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014553",
  "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|Tuberculosis Research and Epidemiology"
    ],
    [
      "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/Immune cells/White blood cells/Macrophages"
    ],
    [
      "plos",
      "/Biology and life sciences/Immunology/Immune cells/White blood cells/Macrophages"
    ],
    [
      "plos",
      "/Biology and life sciences/Molecular biology/Molecular biology techniques/Molecular probe techniques/Immunoblot analysis"
    ],
    [
      "plos",
      "/Biology and life sciences/Molecular biology/Molecular biology techniques/Transfection"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Bacteria/Actinobacteria/Mycobacterium tuberculosis"
    ],
    [
      "plos",
      "/Medicine and health sciences/Immunology/Immune cells/White blood cells/Macrophages"
    ],
    [
      "plos",
      "/Medicine and health sciences/Medical conditions/Infectious diseases/Bacterial diseases/Tuberculosis"
    ],
    [
      "plos",
      "/Medicine and health sciences/Medical conditions/Tropical diseases/Tuberculosis"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Intracellular pathogens"
    ],
    [
      "plos",
      "/Research and analysis methods/Biological cultures/Cell lines/293T cells"
    ],
    [
      "plos",
      "/Research and analysis methods/Microscopy/Light microscopy/Fluorescence recovery after photobleaching"
    ],
    [
      "plos",
      "/Research and analysis methods/Molecular biology techniques/Molecular probe techniques/Immunoblot analysis"
    ],
    [
      "plos",
      "/Research and analysis methods/Molecular biology techniques/Transfection"
    ]
  ],
  "openalex": "W7211949038",
  "pdf_url": "https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1014553&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-08",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/6zb4416swc3hz.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:56Z",
      "native_id": "10.1371/journal.ppat.1014553",
      "source": "plos",
      "url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014553"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "plos:molecular biology",
      "subfield": "molecular-biology"
    },
    {
      "field": "biology",
      "origin": "plos:cell biology",
      "subfield": "cell-biology"
    },
    {
      "field": "biology",
      "origin": "plos:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "TRIM21 blocks DDX3X-driven stress granule formation during Mycobacterium tuberculosis infection via a non-canonical E3 ligase mechanism",
  "title_text": "TRIM21 blocks DDX3X-driven stress granule formation during Mycobacterium tuberculosis infection via a non-canonical E3 ligase mechanism",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:56Z",
  "url": "https://research.draconitic.com/paper/6zb4416swc3hz",
  "venue": "PLOS Pathogens",
  "versions": []
}