{
  "abstract": "BackgroundMycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB) is able to survive and replicate within host cells of the myeloid cell lineage, a critical step in the development of active TB, achieved through multiple immune evasion mechanisms. TRPML1 (Mucolipin 1), a non-selective Ca2+ ion channel belonging to the TRP superfamily, is predominantly expressed in innate immune cells and is localized intracellularly along the endosomal–lysosomal continuum. TRPML1-mediated Ca2+ signalling is vital for lysosomal biogenesis and trafficking processes essential for effective immune responses. The mechanisms regulating TRPML1 channel function in myeloid cells during mycobacterial infection remain poorly characterized.MethodsDuring in vitro infection, TRPML1 expression was modulated in a time-dependent manner by Mtb and M. bovis BCG in murine macrophages, as well as in human neutrophils (PMNs) and macrophages (MDMs). Using pharmacological modulation of TRPML1 channel activity, we observed alterations in intracellular Ca2+ concentrations following Mtb infection.ResultsHere, we describe distinct TRPML1 expression patterns in granulomas from TB patients who had completed treatment for active TB, suggesting a potential role for TRPML1 in pathogenesis. We further demonstrate that Mtb infection is associated with altered TRPML1 expression and intracellular Ca2+ homeostasis, accompanied by changes in ROS production, necrotic cell death and enhanced mycobacterial survival within host cells. Treatment of PMN-MDM cocultures with a TRPML1 antagonist, but not an agonist, was associated with increased reactive oxygen species (ROS) levels and necrotic cell death.DiscussionHere, we show that Mtb-mediated disruption of TRPML1 function is associated with altered intracellular Ca2+ homeostasis and may contribute to impaired phagosome maturation, a process previously linked to TRPML1-dependent endolysosomal function, thereby potentially favoring mycobacterial survival within host cells. These findings suggest that Mtb-induced alterations in TRPML1 associated cellular Ca²⁺ homeostasis may impair Ca²⁺-dependent ROS production and cell death, potentially affecting intracellular Mtb survival. Our findings support a role for TRPML1 in maintaining myeloid cell Ca²⁺ homeostasis and suggest that TRPML1 may contribute to the innate immune response to Mtb infection.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Original Research",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "Priya Ghosh"
    },
    {
      "name": "Jacqueline Eich"
    },
    {
      "name": "Tobias Dallenga"
    },
    {
      "name": "Norbert Reiling"
    },
    {
      "name": "Barbara Kalsdorf"
    },
    {
      "name": "Srikanth Karnati"
    },
    {
      "name": "Ulrich E. Schaible"
    },
    {
      "name": "Avinash Sonawane"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8zcz2zj6ga81w.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1962333",
  "fulltext_url": null,
  "id": "8zcz2zj6ga81w",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1962333",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "feed-journal",
      "biology/immunology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-09",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/8zcz2zj6ga81w.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T06:20:07Z",
      "native_id": "10.3389/fimmu.2026.1962333",
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      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1962333"
    },
    {
      "first_seen": "2026-11-09T12:22:59Z",
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      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1962333/full"
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  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "feed-journal:biology/immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Deciphering the role of TRPML1-mediated calcium homeostasis in innate immune cell responses during Mycobacterium tuberculosis infection",
  "title_text": "Deciphering the role of TRPML1-mediated calcium homeostasis in innate immune cell responses during Mycobacterium tuberculosis infection",
  "type": "peer-reviewed",
  "updated_at": "2026-11-10T00:21:33Z",
  "url": "https://research.draconitic.com/paper/8zcz2zj6ga81w",
  "venue": "Frontiers in Immunology",
  "versions": []
}