Transcriptome Analysis Identifies the Crosstalk between Dendritic and Natural Killer Cells in Human Cutaneous Leishmaniasis

Skin ulcers of cutaneous leishmaniasis (CL) are characterized by a localized inflammatory response mediated by innate and adaptive immune cells, including dendritic cells (DC) and natural killer (NK) cells. Bidirectional interactions between DCs and NK cells contribute to tailor leishmaniasis outcome. Despite advances in the Leishmania biology field in recent decades, the mechanisms involved in DC/NK-mediated control of Leishmania sp. pathogenesis as well as the cellular and molecular players involved in such interaction remain unclear. The present study sought to investigate canonical pathways associated with CL arising from Leishmania braziliensis infection. Initially, two publicly available microarray datasets of skin biopsies from active CL lesions were analyzed, and five pathways were identified using differentially expressed genes. The Crosstalk between DCs and NK cells pathway was notable due to a high number of modulated genes. The molecules significantly involved in this pathway were identified, and our findings were validated in newly obtained CL biopsies. We found increased expression of TLR4, TNFRSF1B, IL-15, IL-6, CD40, CCR7, TNF and IFNG, confirming the analysis of publicly available datasets. These findings reveal the crosstalk between DCs and NK cells as a potential pathway to be further explored in the pathogenesis of CL, especially the expression of CCR7, which is correlated with lesion development.

Automated summary

Skin ulcers in cutaneous leishmaniasis (CL) are influenced by the interaction between dendritic cells (DCs) and natural killer (NK) cells. This study identified the crosstalk between DCs and NK cells pathway as a potential pathway involved in the pathogenesis of CL, with molecules such as TLR4, TNFRSF1B, IL-15, IL-6, CD40, CCR7, TNF, and IFNG playing significant roles. The expression of CCR7, in particular, was found to be correlated with lesion development.