The metabolic signature of inflammatory skin-imprinted eosinophils accounts for the chronicity of Leishmania mexicana infections [Day14]

Eosinophils exert antimicrobial, cytotoxic and immunoregulatory effects, but their function in cutaneous tissue still remains poorly understood. Here, we used a mouse model of chronic cutaneous leishmaniasis caused by the protozoan parasite Leishmania (L.) mexicana to investigate the functional role and transcriptomic signature of eosinophils in the skin. In C57BL/6 wild-type mice, L. mexicana induced local and systemic eosinophilia that was dependent on type 2 innate lymphoid cells and interleukin-5. Genetic and pharmacological depletion of eosinophils led to clinical resolution of disease, which was accompanied by a more pronounced Th1 and M1-like macrophage response. Bioinformatic analyses revealed a novel inflammatory and tissue-specific transcriptional trajectory in skin-infiltrating eosinophils. Skin-imprinted eosinophils strongly expressed the high-affinity glucose transporter 3 (Slc2a3), deprived the environment of glucose and directly impeded the function of Th1 cells. Together, our results demonstrate that the chronicity of L. mexicana infection is linked to inflammatory eosinophils and their metabolic signature Overall design: 10x C57BL/6N mice were infected subcutaneously in the skin of both hind feet with 3 x 106 Leishmania mexicana (MNYC/BZ/62/M379) in 50 µl of PBS for 14 days. A scRNA-Seq was performed on total viable foot skin, bone marrow and blood using BD Rhapsody.