The outcome of Leishmania infection is strongly influenced by the host’s genetic background. BALB/c mice are susceptible to Leishmania infection, while C57BL/6 mice show discrete resistance. Central to the fate of the infection is the availability of l-arginine and the related metabolic processes in the host and parasite. Depending on l-arginine availability, nitric oxide synthase 2 (NOS2) of the host cell produces nitric oxide (NO) controlling the parasite growth. On the other hand, Leishmania can also use host l-arginine for the production of polyamines through its own arginase activity, thus favouring parasite replication. Considering RNA-seq data, we analysed the dual modulation of host and parasite gene expression of BALB/c or C57BL/6 mouse bone marrow-derived macrophages (BMDMs) after 4 h of infection with Leishmania amazonensis wild-type (La-WT) or L. amazonensis arginase knockout (La-arg-). We identified 12 641 host transcripts and 8282 parasite transcripts by alignment analysis with the respective Mus musculus and L. mexicana genomes. The comparison of BALB/c_La-arg- versus BALB/c_La-WT revealed 233 modulated transcripts, with most related to the immune response and some related to the amino acid transporters and l-arginine metabolism. In contrast, the comparison of C57BL/6_La-arg- vs. C57BL/6_La-WT revealed only 30 modulated transcripts, including some related to the immune response but none related to amino acid transport or l-arginine metabolism. The transcriptome profiles of the intracellular amastigote revealed 94 modulated transcripts in the comparison of La-arg-_BALB/c vs. La-WT_BALB/c and 45 modulated transcripts in the comparison of La-arg-_C57BL/6 vs. La-WT_C57BL/6. Taken together, our data present new insights into the impact of parasite arginase activity on the orchestration of the host gene expression modulation, including in the immune response and amino acid transport and metabolism, mainly in susceptible BALB/c-infected macrophages. Moreover, we show how parasite arginase activity affects parasite gene expression modulation, including amino acid uptake and amastin expression.

中文翻译：

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双转录组分析揭示了受利什曼原虫精氨酸酶和宿主遗传背景影响的差异基因表达调节。

利什曼原虫感染的结果受宿主遗传背景的强烈影响。BALB/c 小鼠易受利什曼原虫感染，而 C57BL/6 小鼠表现出不连续的抵抗力。中央对感染的命运的可用性升精氨酸，并在主机和寄生虫有关的代谢过程。根据l-精氨酸的可用性，宿主细胞的一氧化氮合酶 2 (NOS2) 产生控制寄生虫生长的一氧化氮 (NO)。另一方面，利什曼原虫也可以使用宿主l-精氨酸通过其自身的精氨酸酶活性生产多胺，从而有利于寄生虫复制。考虑RNA-SEQ的数据，我们感染4小时后，分析的BALB / c或C57BL / 6小鼠的骨髓来源的巨噬细胞（的BMDM）的主机和寄生虫的基因表达的双调制利什曼原虫亚马孙野生型（拉-WT）或L. amazonensis精氨酸酶敲除 ( La -arg - )。我们通过与Mus musculus和L. mexicana基因组的比对分析确定了 12 641 个宿主转录本和 8282 个寄生虫转录本。BALB/c_ La -arg - 与BALB/c_ 的比较La -WT 揭示了 233 个受调节的转录物，其中大多数与免疫反应有关，一些与氨基酸转运蛋白和l-精氨酸代谢有关。与此相反，C57BL的比较/ 6_拉-arg - 对C57BL / 6_拉-WT显示只有30调制转录，包括一些与涉及氨基酸运输或免疫应答但没有升精氨酸代谢。胞内无鞭毛体的转录谱分析结果发现在所述比较94个调制转录的La -arg - _BALB / C与拉-WT_BALB / c和45个调制的转录物的比较拉-Arg- _C57BL/6与 La -WT_C57BL/6。综上所述，我们的数据为寄生虫精氨酸酶活性对宿主基因表达调节协调的影响提供了新的见解，包括免疫反应和氨基酸转运和代谢，主要是在易感的 BALB/c 感染的巨噬细胞中。此外，我们展示了寄生虫精氨酸酶活性如何影响寄生虫基因表达调节，包括氨基酸摄取和 amstin 表达。