There is currently a dearth of knowledge regarding skin human response to anthroponotic cutaneous leishmaniasis (CL) caused by L. tropica. We employed RNA-seq combined with a system biology approach to defined functional transcriptional pathways in skin biopsies from ulcerative CL (UCL) and non-ulcerative CL (NUCL) patients.
The patients had been collected in the CL clinic at Medical School, Mashhad, Iran, which lesions patients classified based on their clinical presentation as UCLs with the ulcerated epidermis and NUCLs with intact epidermis. The skin biopsies driven from patients’ lesions and healthy individuals were collected to subject for RNA isolation. NextSeq 500 platform was applied for RNA-seq and subsequent analysis to pinpoint shared or exclusive immunological pathways in skin lesions of UCLs and NUCLs.
A gene set enrichment analysis (GSEA) was performed on the gene expression data from the UCL and NUCL lesions compared with the healthy skins by a Reactome database. Results from GSEA identified 100 and 49 enriched pathways (adjusted p<0.05) in the lesions of UCL and the NUCL groups, respectively. Of these, 45 biological pathways were common between the skin lesions of the UCL and NUCL patients. Most of the common enriched pathways were clustered in five main groups, including “TLR pathways”, “IFNs signaling”, “TCR complex”, “FcγR-dependent phagocytosis” and “Notch signaling”. Whereas, 55 enriched pathways were unique for the UCL lesions that several of the highly enriched pathways were related to gene expression, epigenetic regulation and signal transduction pathways. In the NUCLs, four unique pathways were associated with nuclear structure and mitotic anaphase.
Our findings indicate that several transcriptional pathways involved in the inflammatory response in the UCL and NUCL lesions. These results enhance our understanding of human skin response to CL caused by L. tropica, and may inform rational design of novel intervention strategies to counter CL in humans.