Transcriptome analysis of dermal fibroblasts derived from VL and PKDL patients reveal disease specific gene expression and pathological regulation.

BACKGROUND: Post kala-azar dermal leishmaniasis (PKDL), a dermal form of the disease, occurs in some of the visceral leishmaniasis (VL) patients following treatment. The PKDL disease mechanism is yet not clearly understood.

OBJECTIVES: Here we have studied the role of dermal fibroblasts in VL and PKDL disease mechanism.

METHODS: Dermal fibroblasts were grown from skin biopsy explants collected from individual VL & PKDL patients and healthy controls. Fibroblasts from third passage were subjected to RNA-Seq for analyzing differentially-expressed genes (DEGs). Significantly important genes were further validated by RT-PCR and ELISA.

RESULTS: Transcriptome analysis of PKDL vs VL identified 516 DEGs (263 were overrepresented and 253 were underrepresented in PKDL). Among the top Hub-genes, MMP2, IL1β, CXCL8, IFIH1, NFKB1A, IL6, ISG15 and EGFR were underexpressed and ACTB, HSP90AA1, RAB7A and RPS27A were overexpressed in PKDL compared to VL.

CONCLUSIONS: Our data indicates that PKDL fibroblasts may present antigens through MHC I pathway activating CD8+ T-cell mediated response while the VL fibroblasts express NFκB mediated chemokines, IL1β, IL6 and IL8 resulting in the recruitment of NK-cells and monocytes to the site of infection leading to the clearance of parasite from the skin and visceralization of the disease.