Dual transcriptome analysis reveals differential gene expression modulation influenced by Leishmania arginase and host genetic background.
Dual transcriptome analysis reveals differential gene expression modulation influenced by Leishmania arginase and host genetic background.
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DOI：
10.1099/mgen.0.000427
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发表时间：
2020-09
影响因子：
3.9
通讯作者：
Floeter-Winter LM
中科院分区：
文献类型：
--
作者：
Aoki JI;Muxel SM;Laranjeira-Silva MF;Zampieri RA;Müller KE;Nerland AH;Floeter-Winter LM
利什曼原虫感染的结果受到宿主遗传背景的强烈影响。BALB/c小鼠对利什曼原虫感染易感，而C57 BL/6小鼠显示离散的抗性。感染的命运的中心是L-精氨酸的可用性和宿主和寄生虫中的相关代谢过程。取决于L-精氨酸的可用性，宿主细胞的一氧化氮合酶2（NOS 2）产生控制寄生虫生长的一氧化氮（NO）。另一方面，利什曼原虫也可以利用宿主L-精氨酸通过其自身的精氨酸酶活性产生多胺，从而有利于寄生虫复制。考虑到RNA-seq数据，我们分析了BALB/c或C57 BL/6小鼠骨髓源性巨噬细胞（BMDM）感染亚马逊利什曼原虫野生型（La-WT）或L. amazonensisarg酶基因敲除（La-arg-）。 通过与小家鼠（Mus musculus）和L.墨西哥的基因组BALB/c_La-arg-与BALB/c_La-WT的比较显示了233个受调节的转录本，其中大部分与免疫应答相关，一些与氨基酸转运蛋白和l-精氨酸代谢相关。相比之下，C57 BL/6_La-arg-与C57 BL/6_La-WT的比较显示仅30个调节的转录物，包括一些与免疫应答相关的转录物，但与氨基酸转运或l-精氨酸代谢无关。细胞内无鞭毛体的转录组谱显示，在La-arg-_BALB/c与La-WT_BALB/c的比较中有94个调节的转录物，在La-arg-_C57BL/6与La-WT_C57 BL/6的比较中有45个调节的转录物。两者合计，我们的数据提出了新的见解寄生虫脱氢酶活性对宿主基因表达调控的编排的影响，包括在免疫应答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。此外，我们还展示了寄生虫脱氢酶活性如何影响寄生虫基因表达调控，包括氨基酸摄取和无鞭毛体蛋白表达。
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.
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影响因子：
3.8
作者：
Aoki, Juliana Ide;Muxel, Sandra Marcia;Floeter-Winter, Lucile Maria
通讯作者：
Floeter-Winter, Lucile Maria
影响因子：
3.8
作者：
Fernandez-Figueroa, Edith A.;Rangel-Escareno, Claudia;Becker, Ingeborg
通讯作者：
Becker, Ingeborg
影响因子：
2.4
作者：
Gregory, DJ;Olivier, M
通讯作者：
Olivier, M
影响因子：
3.8
作者：
Aoki, Juliana Ide;Coelho, Adriano Cappellazzo;Cotrim, Paulo Cesar
通讯作者：
Cotrim, Paulo Cesar
影响因子：
3.8
作者：
Aoki, Juliana Ide;Muxel, Sandra Marcia;Floeter-Winter, Lucile Maria
通讯作者：
Floeter-Winter, Lucile Maria