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Cited by 28Research on Leishmaniasis StudiesT-cell and B-cell ImmunologyLeprosy Research and Treatment

Regulatory T cells control Staphylococcus aureus and disease severity of cutaneous leishmaniasis

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Singh, Tej Pratap, Farias Amorim, Camila, Lovins, Victoria M., Bradley, Charles W., Carvalho, Lucas P., Carvalho, Edgar M., Grice, Elizabeth A., Scott, Phillip·2023·Journal of Experimental Medicine
DOI 10.1084/jem.20230558PMC PMC10561556
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Abstract

Cutaneous leishmaniasis causes alterations in the skin microbiota, leading to pathologic immune responses and delayed healing. However, it is not known how these microbiota-driven immune responses are regulated. Here, we report that depletion of Foxp3+ regulatory T cells (Tregs) in Staphylococcus aureus–colonized mice resulted in less IL-17 and an IFN-γ–dependent skin inflammation with impaired S. aureus immunity. Similarly, reducing Tregs in S. aureus–colonized and Leishmania braziliensis–infected mice increased IFN-γ, S. aureus, and disease severity. Importantly, analysis of lesions from L. braziliensis patients revealed that low FOXP3 gene expression is associated with high IFNG expression, S. aureus burden, and delayed lesion resolution compared to patients with high FOXP3 expression. Thus, we found a critical role for Tregs in regulating the balance between IL-17 and IFN-γ in the skin, which influences both bacterial burden and disease. These results have clinical ramifications for cutaneous leishmaniasis and other skin diseases associated with a dysregulated microbiome when Tregs are limited or dysfunctional.

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  • IFN-γ induces apoptosis in epithelial cells and fibroblasts and can enhance cell-mediated cytotoxicity.

    “Since IFN-γ induces apoptosis in epithelial cells and fibroblasts and can enhance cell-mediated cytotoxicity [21–23], we examined if the increased production of IFN-γ in C. auris-infected mice might promote increased cell death and enhance fungal burden.”

    From The Emerging Fungal Pathogen Candida auris Induces IFNγ to Colonize the Skin (2025) · cites this paper as [22]

    The Results section (“IFN-γ mediates increased inflammation, epidermal damage, and S. aureus burden”; page unavailable) states that IFN-γ induces keratinocyte apoptosis and can enhance cell-mediated cytotoxicity. It also reports increased death of S. aureus–exposed keratinocytes treated with IFN-γ. Keratinocytes are epithelial cells, but the cited paper does not support the added claim about fibroblast apoptosis. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • IFN-γ drives apoptosis of epithelial cells and fibroblasts and disrupts barrier integrity.

    “Secondly, IFN-γ drives apoptosis of epithelial cells and fibroblasts and disrupts barrier integrity [117–119].”

    From Host–Candida auris interactions in the skin (2026) · cites this paper as [118]

    The Results section ('IFN-γ mediates increased inflammation, epidermal damage, and S. aureus burden'; page not provided) reports IFN-γ-associated epidermal cell death and damage, while the Discussion says high IFN-γ promotes skin-barrier disruption and describes keratinocyte apoptosis in other contexts. Our copy does not support the claim that IFN-γ drives fibroblast apoptosis, and this study's cell-death experiments do not establish apoptosis specifically. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Singh, T. P., Farias Amorim, C., Lovins, V. M., Bradley, C. W., Carvalho, L. P., Carvalho, E. M., Grice, E. A., & Scott, P.
Affiliations
  • University of Pennsylvania (US)
  • School of Veterinary Medicine, University of Pennsylvania 1 Department of Pathobiology, , Philadelphia, PA, USA
  • Universidade Federal da Bahia (BR)
Corresponding author
Scott, Phillip
ORCID
Venue
Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2023-10-09
Volume
220
Issue
12
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.20230558
PMC
PMC10561556
OpenAlex
W4387439667
Cited by
28
References
6
Citations by year
2026: 7 · 2025: 13 · 2024: 7 · 2023: 1
FWCI
7.17
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of Experimental Medicine (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • Arca - Repositório Institucional da Fiocruz (submittedVersion, other-oa)
Funders
National Institutes of Health (RO1AI143790, RO1AI149456, P50 AI030639)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Research on Leishmaniasis Studies
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Infectious Diseases › Leprosy Research and Treatment
Keywords
regulatory T cells, Foxp3, cutaneous leishmaniasis, Staphylococcus aureus, Leishmania braziliensis, skin microbiome, IL-17, interferon-gamma, skin inflammation, disease severity, bacterial colonization, Foxp3 expression, lesion resolution
MeSH terms
Animals, Humans, Staphylococcal Infections, Staphylococcus aureus, Leishmaniasis, Cutaneous, Interleukin-17, T-Lymphocytes, Regulatory, Mice, Forkhead Transcription Factors, Patient Acuity

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