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