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

2023/10/09 by Tej Pratap Singh, Camila Farias Amorim, Victoria Lovins +6 · 11 citations
Medicine · Immunology and Microbiology · #Research on Leishmaniasis Studies #Urticaria and Related Conditions #Toxin Mechanisms and Immunotoxins

paper · pdf · doi:10.1084/jem.20230558

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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• Malnutrition exacerbates pathogenesis of Lutzomyia longipalpis sand fly-transmitted Leishmania donovani. [europepmc]
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• Establishment of a transdermal infection model with Leishmania amazonensis. [europepmc]
• Host-Candida auris interactions in the skin. [europepmc]
• Revisiting the past in light of current knowledge on γδ T cells in leishmaniasis. [europepmc]

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