Humanised Mice in Cutaneous Leishmaniasis-T-Cell Recruitment Into Human Skin Transplants After Leishmania major Infection.

Abstract

Treatment against leishmaniasis is associated with severe side effects, high costs, and parasitic resistance. Preclinical models such as humanised mice would aid therapeutic improvement or the development of a vaccine. We developed a model in which human skin transplants on immunodeficient mice are infected with Leishmania major. Parasite inoculation of the skin transplant led to a robust infection with increasing numbers of parasites in the skin and visceral organs. In addition, intraperitoneally co-administered allogeneic peripheral blood mononuclear cells (PBMCs) were strongly recruited to skin lesions, with ≥ 65% of the cells being positive for anti-human CD45; we identified ~20% CD4and ~50% CD8human T cells. The number of skin-resident macrophages or dendritic cells was unaltered compared to healthy skin prior to transplantation, and PBMC administration did not alter their numbers. Together, we show that parasitic infection provides a strong inflammatory signal that leads to recruitment of T cells into skin transplants. The presence of antigen-presenting cells in the transplants-as an important prerequisite for proper APC-T-cell interaction-recreates a fully human skin microenvironment that allows for stroma/immune cell interactions upon infection. This model may be of high interest to researchers interested in translating skin research questions into the human system in vivo.