{
  "abstract": "Macrophage activation is essential for innate immunity and antimicrobial defense. We show that Enterococcus faecalis suppresses macrophage activation through lactic-acid-mediated acidification of the extracellular environment, enabling pathogen persistence. E. faecalis- derived lactic acid acts via the lactate transporter monocarboxylate transporter 1 (MCT-1) and the sensor GPR81 to initiate complementary mechanisms that collaboratively reduce nuclear factor κB (NF-κB) activity. Lactic acid acts through MCT-1 to inhibit extracellular signal-regulated kinase and STAT3 phosphorylation, leading to reduced levels of the adaptor MyD88 involved in NF-κB activation. Lactic acid signaling to GPR81 induces phosphorylation of the transcription factor YAP, ultimately attenuating NF-κB signaling. A bacterial mutant lacking lactate dehydrogenase is unable to acidify the environment and thus fails to inhibit NF-κB. In a murine wound infection model, lactic-acid-driven immunosuppression enables prolonged E. faecalis persistence and enhances the fitness of co-infecting bacteria such as Escherichia coli . These findings reveal how bacterial lactic acid subverts innate immunity to support chronic and polymicrobial infections. • E. faecalis suppresses macrophage activation via lactic acid release • Lactic acid signals through MCT-1 and GPR81 to inhibit NF-κB • Lactic-acid-driven immunosuppression promotes persistence and polymicrobial infection da Silva et al. show that Enterococcus faecalis -derived lactic acid suppresses macrophage NF-κB activation via MCT-1 and GPR81 signaling. This lactic-acid-driven immunosuppression promotes bacterial persistence and enhances polymicrobial infection in vivo .",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "Ronni A.G. da Silva"
    },
    {
      "name": "Brenda Yin Qi Tien"
    },
    {
      "name": "Patrick Hsien Neng Kao"
    },
    {
      "name": "Haris Antypas"
    },
    {
      "name": "Cenk Celik"
    },
    {
      "name": "Ai Zhu Casandra Tan"
    },
    {
      "name": "Muhammad Hafiz Ismail"
    },
    {
      "name": "Guangan Hu"
    },
    {
      "name": "Kelvin Kian Long Chong"
    },
    {
      "name": "Guillaume Thibault"
    },
    {
      "name": "Jianzhu Chen"
    },
    {
      "name": "Kimberly A. Kline"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9f60f6n4hjwg3.bib",
  "cited_by": 12,
  "doi": "10.1016/j.chom.2026.01.002",
  "fulltext_url": null,
  "id": "9f60f6n4hjwg3",
  "issns": [
    "1931-3128"
  ],
  "landing_url": "https://hal.science/hal-05770379v1",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "hal",
      "1.sdv.bc"
    ],
    [
      "openalex",
      "2403|Immune Response and Inflammation"
    ]
  ],
  "openalex": "W7125808128",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-30",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/9f60f6n4hjwg3.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:43Z",
      "native_id": "hal-05770379",
      "source": "hal",
      "url": "https://hal.science/hal-05770379v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "hal:1.sdv.bc",
      "subfield": "cell-biology"
    }
  ],
  "title": "Enterococcus faecalis-derived lactic acid suppresses macrophage activation to facilitate persistent and polymicrobial wound infections",
  "title_text": "Enterococcus faecalis-derived lactic acid suppresses macrophage activation to facilitate persistent and polymicrobial wound infections",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:43Z",
  "url": "https://research.draconitic.com/paper/9f60f6n4hjwg3",
  "venue": "Cell Host and Microbe",
  "versions": []
}