Enhanced translational activity is linked to lymphatic endothelial cell activation in cutaneous leishmaniasis 4267

Abstract Description Cutaneous leishmaniasis (CL) is a significant public health problem leading to permanently disfiguring skin lesions caused by Leishmania parasites. Lesion severity is dictated by an excessive host inflammatory response that prevents healing. Using single-cell RNA sequencing data, we identified upregulation of antigen presentation pathways including MHC-I, MHC-II, and immunoproteasome transcripts in dermal LECs from Leishmania major-infected mice compared to naive controls. LECs also displayed increased expression of guanylate binding proteins and interferon-inducible genes, indicative of immune activation. Moreover, our results demonstrate that LECs in leishmanial lesions exhibited heightened translational activity relative to LECs from uninflamed ears, and LEC translational activity was highest in activated LECs. LEC translational activity exceeded that of other cell types within the lesion. Validating the transcriptomic data, LECs in lesions expressed elevated MHC-II and programmed death-ligand 1 (PDL-1), indicating their potential role in antigen presentation. Functional assays using DQ-OVA established that LECs from leishmanial lesions efficiently uptake and process antigens, highlighting their capability as antigen presenting cells in the inflamed dermal microenvironment. Overall, our study unveils the activation status of LECs in leishmanial lesions, shedding light on their potential role in shaping local immunity and inflammation in a variety of skin diseases. Funding Sources NIGMS P20-GM103429, NIGMS P20-GM103625, NIGMS T32 training grant GM106999, NCATS TL1 TR003109 and UL1 TR003107, NIGMS P20-GM121293, and NSF OIA-1946391 Topic Categories Antigen and Dendritic Cell Processing, Presentation, and Biology (AGDC)