Cutaneous leishmaniasis is caused by infection with the protozoan parasite Leishmania, which resides intracellularly in dermal macrophages (Mø), producing lesions. The skin lesions are characterized by proinflammatory cytokines and growth factors as well as inflammatory hypoxia, creating a stressful microenvironment for Mø. Of importance, not all Mø in lesions harbor parasites. To distinguish the influence of the parasite from the inflammatory microenvironment after Leishmania major (LM) infection on the Mø, we performed single-cell RNA sequencing and compared Mø associated with LM transcripts (or ‘infected' Mø) with Mø not associated with LM transcripts (or ‘bystander' Mø) within the lesions. Our findings show coordinated lysosomal expression and regulation signaling with increased cathepsin and H⁺-ATPase transcripts are upregulated in infected compared with bystander Mø. Additionally, eukaryotic initiation factor 2 (EIF2) signaling is downregulated in infected compared with bystander Mø, which includes many small and large ribosomal subunit (Rps and Rpl) transcripts being decreased in Mø harboring parasites. Furthermore, we also find EIF2 signaling including EIF, Rps, and Rpl transcripts being downregulated in bystander Mø compared with Mø from naïve skin. These data suggest that both the parasite and the inflammatory host microenvironment affect the transcription of ribosomal machinery in lesional Mø, thereby potentially affecting the ability of these cells to perform translation, protein synthesis, and thus function. Altogether, these results suggest that both the parasite and host inflammatory microenvironment independently drive transcriptional remodeling in Mø during LM infection in vivo.

皮肤利什曼病是由原生动物寄生虫利什曼原虫感染引起的，该寄生虫存在于真皮巨噬细胞 (Mø) 的细胞内，产生病变。皮肤病变的特点是促炎细胞因子和生长因子以及炎症缺氧，为 Mø 创造了一个充满压力的微环境。重要的是，并非所有病变处的 Mø 都含有寄生虫。区分大型利什曼原虫感染后寄生虫与炎症微环境的影响(LM) 感染 Mø，我们进行了单细胞 RNA 测序，并将与病灶内 LM 转录本相关的 Mø（或“感染的”Mø）与与病灶内 LM 转录本无关的 Mø（或“旁观者”Mø）进行了比较。^{我们的研究结果表明，随着组织蛋白酶和 H +}的增加，溶酶体表达和调节信号协调一致-与旁观者 Mø 相比，感染者的 ATPase 转录本上调。此外，与旁观者 Mø 相比，感染者的真核起始因子 2 (EIF2) 信号传导下调，其中包括许多大小核糖体亚基（Rps 和 Rpl）转录本在寄生寄生虫的 Mø 中减少。此外，我们还发现与天然皮肤的 Mø 相比，旁观者 Mø 中的 EIF2 信号传导（包括 EIF、Rps 和 Rpl 转录本）下调。这些数据表明，寄生虫和炎症宿主微环境都会影响病变 Mø 中核糖体机器的转录，从而可能影响这些细胞执行翻译、蛋白质合成和功能的能力。共，