Enhanced Translational Activity Is Linked to Lymphatic Endothelial Cell Activation in Cutaneous Leishmaniasis

Area of Science:

• Immunology
• Cell Biology
• Dermatology

Background:

• Cutaneous leishmaniasis (CL) causes disfiguring skin lesions due to uncontrolled inflammation.
• The role of lymphatic endothelial cells (LECs) in CL pathogenesis is not fully understood.

Purpose of the Study:

• To investigate the transcriptional and translational activity of LECs during murine CL.
• To determine the function of LECs as antigen-presenting cells in leishmaniasis.

Main Methods:

• Single-cell RNA sequencing of dermal LECs from infected and naive mice.
• Flow cytometry and in vivo puromycin incorporation to assess protein synthesis.
• Functional assays using DQ-ovalbumin to evaluate antigen uptake and processing.

Main Results:

• LECs in CL lesions upregulate antigen presentation pathways (MHC-I, MHC-II) and interferon-inducible genes.
• LECs exhibit heightened translational activity, exceeding other cell types in the lesion microenvironment.
• LECs efficiently uptake and process antigens, confirming their role as antigen-presenting cells.

Conclusions:

• LECs are activated in CL lesions, contributing to local immune responses.
• LECs play a significant role in antigen presentation within the inflamed dermal microenvironment.
• Understanding LEC activation in CL offers insights into various skin diseases.