Mycobacterium tuberculosissulfolipid-1 (Sl-1) increases the excitability of mouse and human TRPV1-positive sensory neurons in a YM254890-reversible fashion Article Swipe
Dhananjay K. Naik
,
Felipe Espinosa
,
Ifunanya M. Okolie
,
Kubra F. Naqvi
,
Giang Nguyen
,
Cody R. Ruhl
,
Sven Kroener
,
Gregory Dussor
,
Michael U. Shiloh
,
Theodore J. Price
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.06.28.662105
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.06.28.662105
Cough is a hallmark sign of tuberculosis and key driver of transmission. While traditionally attributed to host-driven inflammation, we previously demonstrated that Mycobacterium tuberculosis lipid extract (Mtb extract) and its component sulfolipid-1 (SL-1) directly activate nociceptive neurons to induce cough in guinea pigs. However, the cellular mechanisms by which Mtb extract and SL-1 modulate nociceptive sensory neurons remain incompletely understood. Here, we show that Mtb extract enhances action potential (AP) generation in mouse nodose nociceptors via an SL-1–dependent mechanism. Using calcium imaging, we found that Mtb extract and SL-1 increased intracellular Ca²⁺ signals in TRPV1⁺ neurons from both mouse nodose and human dorsal root ganglia (hDRG). These Ca²⁺ signals were attenuated by the Gαq/11 pathway inhibitor YM254890, even in the absence of extracellular Ca²⁺, suggesting involvement of intracellular Ca²⁺ stores. Together, these findings indicate that SL-1 engages Gαq/11-coupled pathways to sensitize nociceptors via intracellular Ca 2+ release, providing mechanistic insight into tuberculosis-associated cough and potential targets for therapeutic intervention.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2025.06.28.662105
- https://www.biorxiv.org/content/biorxiv/early/2025/06/29/2025.06.28.662105.full.pdf
- OA Status
- green
- Cited By
- 1
- References
- 59
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4411769078
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4411769078Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1101/2025.06.28.662105Digital Object Identifier
- Title
-
Mycobacterium tuberculosissulfolipid-1 (Sl-1) increases the excitability of mouse and human TRPV1-positive sensory neurons in a YM254890-reversible fashionWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-06-29Full publication date if available
- Authors
-
Dhananjay K. Naik, Felipe Espinosa, Ifunanya M. Okolie, Kubra F. Naqvi, Giang Nguyen, Cody R. Ruhl, Sven Kroener, Gregory Dussor, Michael U. Shiloh, Theodore J. PriceList of authors in order
- Landing page
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https://doi.org/10.1101/2025.06.28.662105Publisher landing page
- PDF URL
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https://www.biorxiv.org/content/biorxiv/early/2025/06/29/2025.06.28.662105.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.biorxiv.org/content/biorxiv/early/2025/06/29/2025.06.28.662105.full.pdfDirect OA link when available
- Concepts
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TRPV1, Nociceptor, Intracellular, Extracellular, Nociception, Mycobacterium tuberculosis, Cell biology, Chemistry, Capsaicin, Neuroscience, Biology, Tuberculosis, Medicine, Biochemistry, Receptor, Transient receptor potential channel, PathologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
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1Total citation count in OpenAlex
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2025: 1Per-year citation counts (last 5 years)
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59Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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