Tissue Specific Dual RNA-Seq Defines Host-Parasite Interplay in Murine Visceral Leishmaniasis Caused by Leishmania donovani and Leishmania infantum.
Tissue Specific Dual RNA-Seq Defines Host-Parasite Interplay in Murine Visceral Leishmaniasis Caused by Leishmania donovani and Leishmania infantum.
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DOI：
10.1128/spectrum.00679-22
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发表时间：
2022-04-27
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
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作者：
在临床前动物模型和人类中，内脏利什曼病与肝脾肿大以及免疫和血液学参数改变有关。采用双RNA-seq方法研究了由婴儿利什曼原虫和多诺瓦利什曼原虫引起的小鼠实验性内脏利什曼病BALB/c小鼠肝脏和脾脏中宿主和寄生虫的转录反应。我们在被感染的脾脏中只发现了4个物种特异性寄生虫表达基因（SSPEGs; log2FC >1, FDR <0.05），在被感染的肝脏中没有。对于宿主转录组，我们在脾脏中发现789个差异表达基因（DEGs; log2FC >1, FDR <0.05）是两种感染共同的，IFNγ信号和补体和凝血级联通路高度富集，另外286个和186个DEGs分别对多诺多氏乳杆菌和婴儿乳杆菌感染具有选择性。其中，乳酸菌感染中氨基酸代谢和PPAR信号通路基因之间存在网络相互作用，乳酸菌感染中il - 1β和脂肪酸转运的正向调控增加，但未观察到通路富集。在肝脏中，与未感染的小鼠相比，感染婴儿乳杆菌或多诺多氏乳杆菌的小鼠有1,939个deg，其中最丰富的途径是IFNγ信号传导、中性粒细胞介导的免疫、补体和凝血、细胞因子趋化因子反应和止血。此外，221个基因在多诺瓦氏乳杆菌中具有选择性，429个基因在婴儿乳杆菌中具有选择性。这些数据表明，宿主对这两种内脏利什曼病感染模型的反应大致相似，并且在两种寄生虫感染中，约10%的宿主deg存在差异。内脏利什曼病（VL）是由两种利什曼原虫引起的，即旧大陆的多诺瓦尼利什曼原虫和新世界和地中海沿岸国家的婴儿利什曼原虫。虽然肝脾肿大、血液和免疫功能改变等主要特征是明显的，但临床表现可能因地理而异，例如巴西的严重出血常与VL相关。虽然多诺瓦氏乳杆菌和婴儿乳杆菌的动物模型已被广泛用于研究疾病发病机制，但这些寄生虫物种如何影响受感染宿主和/或它们如何应对哺乳动物感染的压力的直接并排比较尚未有报道。确定共同和独特的发病途径将是重要的，以确保新的治疗或预防方法将适用于所有形式的VL。
Visceral leishmaniasis is associated with hepato-splenomegaly and altered immune and hematological parameters in both preclinical animal models and humans. We studied mouse experimental visceral leishmaniasis caused by Leishmania infantum and Leishmania donovani in BALB/c mice using dual RNA-seq to investigate the transcriptional response of host and parasite in liver and spleen. We identified only 4 species-specific parasite expressed genes (SSPEGs; log2FC >1, FDR <0.05) in the infected spleen, and none in the infected liver. For the host transcriptome, we found 789 differentially expressed genes (DEGs; log2FC >1, FDR <0.05) in the spleen that were common to both infections, with IFNγ signaling and complement and coagulation cascade pathways highly enriched, and an additional 286 and 186 DEGs that were selective to L. donovani and L. infantum infection, respectively. Among those, there were network interactions between genes of amino acid metabolism and PPAR signaling in L. donovani infection and increased IL1β and positive regulation of fatty acid transport in L. infantum infection, although no pathway enrichment was observed. In the liver, there were 1,939 DEGs in mice infected with either L. infantum or L. donovani in comparison to uninfected mice, and the most enriched pathways were IFNγ signaling, neutrophil mediated immunity, complement and coagulation, cytokine-chemokine responses, and hemostasis. Additionally, 221 DEGs were selective in L. donovani and 429 DEGs in L. infantum infections. These data show that the host response for these two visceral leishmaniasis infection models is broadly similar, and ∼10% of host DEGs vary in infections with either parasite species. IMPORTANCE Visceral leishmaniasis (VL) is caused by two species of Leishmania parasites, L. donovani in the Old World and L. infantum in the New World and countries bordering the Mediterranean. Although cardinal features such as hepato-splenomegaly and alterations in blood and immune function are evident, clinical presentation may vary by geography, with for example severe bleeding often associated with VL in Brazil. Although animal models of both L. donovani and L. infantum have been widely used to study disease pathogenesis, a direct side-by-side comparison of how these parasites species impact the infected host and/or how they might respond to the stresses of mammalian infection has not been previously reported. Identifying common and distinct pathways to pathogenesis will be important to ensure that new therapeutic or prophylactic approaches will be applicable across all forms of VL.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
3.9
作者：
Aoki JI;Muxel SM;Laranjeira-Silva MF;Zampieri RA;Müller KE;Nerland AH;Floeter-Winter LM
通讯作者：
Floeter-Winter LM
影响因子：
16.6
作者：
Baker N;Catta-Preta CMC;Neish R;Sadlova J;Powell B;Alves-Ferreira EVC;Geoghegan V;Carnielli JBT;Newling K;Hughes C;Vojtkova B;Anand J;Mihut A;Walrad PB;Wilson LG;Pitchford JW;Volf P;Mottram JC
通讯作者：
Mottram JC
影响因子：
3.3
作者：
Grace CA;Forrester S;Silva VC;Carvalho KSS;Kilford H;Chew YP;James S;Costa DL;Mottram JC;Costa CCHN;Jeffares DC
通讯作者：
Jeffares DC
影响因子：
3
作者：
Espitia, Claudia M.;Saldarriaga, Omar A.;Melby, Peter C.
通讯作者：
Melby, Peter C.