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. 2023 Oct 9;220(12):e20230558. doi: 10.1084/jem.20230558

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© 2023 Singh et al.

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Figure 8. — Reduced expression of FOXP3 is associated with enhanced IFNG expression and S. aureus burden in human cutaneous leishmaniasis lesions. (A) Dual RNA-seq analyses were performed on lesion biopsies from L. braziliensis–infected patients. The transcripts were first mapped to the human transcriptome, and then unmapped transcripts were aligned to an in-house S. aureus pan-genome to estimate host gene expression and S. aureus transcriptional abundances, respectively. (B) FOXP3 expression in the lesion biopsies. Lesions were subgrouped in FOXP3^high- and FOXP3^low-expressing lesions. Biopsies from 51 patients were used for analysis. Each dot represents a patient. (C) Principal component analysis of FOXP3^high and FOXP3^low samples. Data represent 19 FOXP3^high- and 20 FOXP3^low-expressing biopsies. (D) Differential gene expression analysis was performed between FOXP3^high and FOXP3^low samples. GO accessing biological process was conducted in the list of genes significantly enriched in each group, with cutoff thresholds of FC = 1.5 and adjusted P values = 0.05. Volcano plot with genes differentially expressed, highlighting genes annotated as “response to wounding” (blue) and “regulation of cell killing/cytolysis” (red) from GO analyses. (E) All lesion biopsies in the dataset were classified into two groups: S. aureus–high samples with higher bacterial transcriptional abundances relative to S. aureus–low samples that presented levels comparable to healthy skin. Biopsies from 51 patients were used for analysis. (F and G) FOXP3 and IFNG expression (F), the “Regulation of cell killing/cytolysis” GO term score and the “response to wounding” GO term score (G) in S. aureus–high and S. aureus–low lesions. Data represent 24 S. aureus–low and 27 S. aureus–high expressing biopsies. Two-tailed unpaired Student’s t test with Welch’s correction. (H) Healing time for patients with FOXP3^high- and FOXP3^low-expressing lesions. Green arrows indicate the rounds for antimony treatment. Data represents 19 FOXP3^high- and 20 FOXP3^low-expressing biopsies. Gehan-Breslow-Wilcoxon test. *P < 0.05 and **P < 0.01.