Distinct lymphatic remodeling is associated with healing and non-healing murine cutaneous leishmaniasis

Abstract Cutaneous leishmaniasis (CL) is the spectrum of diseases caused by Leishmaniaparasites endemic to tropical and subtropical regions world causing 1–2 million new cases each year. Based on species infecting parasite host immune status, CL can be self-healing or lead permanent disfiguration. We showed a critical role for lymphatics in wound healing during L. majorinfection C57BL/6 mice, model that replicates most human disease. Specifically, lymphangiogenesis, mediated vascular endothelial growth factor-A (VEGF-A)/vascular factor receptor-2 (VEGFR-2) signaling, required efficient lesion resolution. The lymphatic vasculature regulates response infection, transporting soluble antigen presenting cells lymph nodes engaging an active modulating inflammatory cell exit from site infection. Here, we investigate mice infected with amazonensisand mexicana, non-healing CL. found mediators lymphangiogenesis like VEGF-A VEGF-D are elevated infection but they either delayed not sustained over time which compromises increases vessel dilation compared naïve mice. During Leishmaniainfection find increased associated enhanced disease severity. Taken together, current work suggests attenuated later suggesting impaired remodeling contributes persistent lesions patients COBRE UAMS CMPHIR