Evidence mapPaperPMID 37995657Full record

ArticleCell2023

S. aureus drives itch and scratch-induced skin damage through a V8 protease-PAR1 axis.

Liwen Deng, Flavia Costa, Kimbria J Blake, Samantha Choi, Arundhasa Chandrabalan, Muhammad Saad Yousuf, Stephanie Shiers, Daniel Dubreuil, Daniela Vega-Mendoza, Corinne Rolland and 14 more

Open access · greenAbstract read
In one paragraph

Article in Cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed
36.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

82 citing papers in PubMed, 127 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Article
  4. Epithelial-Dermal Immune Memory: TrackingInternational journal of molecular sciences · 2026
    Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Atopic dermatitis.Nature reviews. Disease primers · 2026
    Review
  12. Emerging point-of-care technologies for bacterial pathogen detection.Journal of Zhejiang University. Science. B · 2026
    Review
  13. An Ex Vivo 'Microorganisms · 2026
    Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review

22 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 9 institutions in 3 countries.

Liwen DengDepartment of Immunology, Harvard Medical School, Boston, MA 02215, USA.
Flavia CostaDepartment of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Kimbria J BlakeDepartment of Immunology, Harvard Medical School, Boston, MA 02215, USA.
Samantha ChoiDepartment of Immunology, Harvard Medical School, Boston, MA 02215, USA.
Arundhasa ChandrabalanDepartment of Physiology and Pharmacology, University of Western Ontario, London, Ontario N6A 5C1, Canada.
Muhammad Saad YousufDepartment of Neuroscience and Center for Advanced Pain Studies, University of Texas at Dallas, Richardson, TX 75080, USA.
Stephanie ShiersDepartment of Neuroscience and Center for Advanced Pain Studies, University of Texas at Dallas, Richardson, TX 75080, USA.
Daniel DubreuilDepartments of Neurology and Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
Daniela Vega-MendozaDivision of Immunology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Corinne RollandIRSD, Université de Toulouse, INSERM, INRAe, ENVT, Université Toulouse III-Paul Sabatier (UPS), Toulouse, France.
Celine DeraisonIRSD, Université de Toulouse, INSERM, INRAe, ENVT, Université Toulouse III-Paul Sabatier (UPS), Toulouse, France.
Tiphaine VoisinDepartment of Immunology, Harvard Medical School, Boston, MA 02215, USA.
Michelle D BagoodDepartment of Dermatology, University of California, San Diego, La Jolla, CA 92093, USA.
Lucia WesemannDepartment of Immunology, Harvard Medical School, Boston, MA 02215, USA.
Abigail M FreyDepartment of Immunology, Harvard Medical School, Boston, MA 02215, USA.
Joseph S PalumboCancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Brian J WaingerDepartments of Neurology and Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
Richard L GalloDepartment of Dermatology, University of California, San Diego, La Jolla, CA 92093, USA.
Juan-Manuel Leyva-CastilloDivision of Immunology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Nathalie VergnolleIRSD, Université de Toulouse, INSERM, INRAe, ENVT, Université Toulouse III-Paul Sabatier (UPS), Toulouse, France.
Theodore J PriceDepartment of Neuroscience and Center for Advanced Pain Studies, University of Texas at Dallas, Richardson, TX 75080, USA.
Rithwik RamachandranDepartment of Physiology and Pharmacology, University of Western Ontario, London, Ontario N6A 5C1, Canada.
Alexander R HorswillDepartment of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Isaac M ChiuDepartment of Immunology, Harvard Medical School, Boston, MA 02215, USA. Electronic address: isaac_chiu@hms.harvard.edu.
Harvard University · USThe University of Texas at Dallas · USUniversité Toulouse III - Paul Sabatier · FRBoston Children's Hospital · USMassachusetts General Hospital · USUniversity of California San Diego · USUniversity of Colorado Anschutz Medical Campus · USWestern University · CACincinnati Children's Hospital Medical Center · US

Funding

Tumor Imaging Metrics CoreP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · 1985 to 2025
$168.8M
ATOPIC DERMATITIS RESEARCH NETWORK LEADERSHIP CENTERUM1AI151958 · NATIONAL JEWISH HEALTH · 2025 to 2025
$7.8M
RESEARCH IN INFECTIOUS DISEASEST32AI007036 · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 1985 to 2025
$2.3M
Cathelicidin in Skin ImmunityR37AI052453 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 to 2025
$1.2M
The Graduate Program in Tropical Infectious DiseasesT32AI049928 · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · 2001 to 2025
$1.2M
Staphylococcus aureus induced itch and neuro-immune signaling in skin infectionsR01AI168005 · HARVARD MEDICAL SCHOOL · 2025 to 2025
$744k
Translation Control of Pain PlasticityR01NS065926 · NINDS · UNIVERSITY OF TEXAS DALLAS · PI Theodore J. Price · 2023 to 2023
$537k
Sex-specific regulation of local translation and chronic pain mechanisms in femalesR01NS102161 · NINDS · UNIVERSITY OF TEXAS DALLAS · PI ARMEN N AKOPIAN, Theodore J. Price · 2022 to 2022
$483k
Microbiome Function in Atopic DermatitisU01AI152038 · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2025 to 2025
$468k
Toward Precision Gene Therapy for Treatment of Severe Pain in Older IndividualsR21AG075419 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Brian Jason Wainger · 2023 to 2023
$204k
Metabolic determinants of Staphylococcus aureus skin colonizationF32AI172080 · UNIVERSITY OF COLORADO DENVER · 2025 to 2025
$80k
NCI NIH HHS P30 CA006516NIAID NIH HHS F32 AI172080NIAID NIH HHS R01 AI153185NIAID NIH HHS R01 AI168005NIAID NIH HHS R37 AI052453NIAID NIH HHS T32 AI007036NIAID NIH HHS T32 AI049928NIAID NIH HHS U01 AI152038NIAID NIH HHS UM1 AI151958NIAMS NIH HHS R01 AR076082NIA NIH HHS R21 AG075419NINDS NIH HHS R01 NS065926NINDS NIH HHS R01 NS102161NINDS NIH HHS R01 NS111929
6 · The paper itself

Abstract

Itch is an unpleasant sensation that evokes a desire to scratch. The skin barrier is constantly exposed to microbes and their products. However, the role of microbes in itch generation is unknown. Here, we show that Staphylococcus aureus, a bacterial pathogen associated with itchy skin diseases, directly activates pruriceptor sensory neurons to drive itch. Epicutaneous S. aureus exposure causes robust itch and scratch-induced damage. By testing multiple isogenic bacterial mutants for virulence factors, we identify the S. aureus serine protease V8 as a critical mediator in evoking spontaneous itch and alloknesis. V8 cleaves proteinase-activated receptor 1 (PAR1) on mouse and human sensory neurons. Targeting PAR1 through genetic deficiency, small interfering RNA (siRNA) knockdown, or pharmacological blockade decreases itch and skin damage caused by V8 and S. aureus exposure. Thus, we identify a mechanism of action for a pruritogenic bacterial factor and demonstrate the potential of inhibiting V8-PAR1 signaling to treat itch.

Indexed as

Peptide HydrolasesPruritusReceptor, PAR-1Staphylococcal InfectionsStaphylococcus aureusAnimalsHumansMicePeptide HydrolasesReceptor, PAR-1itchmicrobePAR1proteinase-activated receptorpruriceptorStaphylococcus aureusV8 protease

Identifiers

PMID37995657
PMCPMC10669764
OpenAlexW4388900284

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.