The origin and functional specialization of dermal macrophages in cutaneous infections have been little studied. In this paper, we show that a strain of Leishmania major (L. major Seidman [LmSd]) that produces nonhealing cutaneous lesions in conventionally resistant C57BL/6 mice was more efficiently taken up by M2-polarized bone marrow (BM)–derived macrophages (BMDMs) in vitro and by mannose receptor (MR)^hi dermal macrophages in vivo compared with a healing strain (L. major Friedlin V1). Both in steady and in T helper type 1 (Th1) cell–driven inflammatory states, the MR^hi dermal macrophages showed M2 characteristics. The dermal macrophages were radio resistant and not replaced by monocytes or adult BM-derived cells during infection, but were locally maintained by IL-4 and IL-10. Notably, the favored infection of M2 BMDMs by LmSd in vitro was MR dependent, and genetic deletion of MR or selective depletion of MR^hi dermal macrophages by anti–CSF-1 receptor antibody reversed the nonhealing phenotype. We conclude that embryonic-derived, MR^hi dermal macrophages are permissive for parasite growth even in a strong Th1-immune environment, and the preferential infection of these cells plays a crucial role in the severity of cutaneous disease.

皮肤巨噬细胞在皮肤感染中的起源和功能专业化研究很少。在本文中，我们显示，M2极化的骨髓（BM）衍生的巨噬细胞可更有效地吸收在常规抗性C57BL / 6小鼠中产生不愈合的皮肤病变的大利什曼原虫（L. major Seidman [LmSd]）菌株（的BMDM）在体外和由甘露糖受体（MR） ^。在真皮的巨噬细胞在体内具有愈合应变（相L.主要Friedlin V1）。在稳态和T辅助1型（Th1）细胞驱动的炎症状态下，MR ^hi真皮巨噬细胞表现出M2特征。真皮巨噬细胞具有抗辐射性，在感染过程中不会被单核细胞或成年BM来源的细胞所替代，但由IL-4和IL-10局部维持。值得注意的是，LmSd在体外对M2 BMDM的有利感染是MR依赖性的，抗CSF-1受体抗体对MR的遗传删除或对MR ^hi真皮巨噬细胞的选择性耗竭可逆转非愈合表型。我们得出的结论是，即使在强Th1免疫环境中，胚胎来源的MR ^hi真皮巨噬细胞也允许寄生虫生长，这些细胞的优先感染在皮肤疾病的严重程度中起着至关重要的作用。