Transcriptomics analysis of Toxoplasma gondii-infected mouse macrophages reveals coding and noncoding signatures in the presence and absence of MyD88.
Transcriptomics analysis of Toxoplasma gondii-infected mouse macrophages reveals coding and noncoding signatures in the presence and absence of MyD88.
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DOI：
10.1186/s12864-021-07437-0
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发表时间：
2021-02-23
期刊：
影响因子：
4.4
通讯作者：
Denkers EY
中科院分区：
文献类型：
--
作者：
Menard KL;Bu L;Denkers EY
弓形虫是一种全球性分布的原生动物寄生虫，在人类中建立终身无症状感染，通常在免疫缺陷期间作为威胁生命的机会致病菌出现。作为一种细胞内微生物，弓形虫从感染开始就与宿主细胞建立了密切的关系。巨噬细胞是感染的目标，它们在早期先天免疫和可能的寄生虫在整个宿主中的传播中是重要的。在这里，我们采用RNA测序的方法来确定宿主和寄生虫的转录反应感染小鼠骨髓源性巨噬细胞（BMDM）。我们将高毒力I型RH菌株和低毒力II型菌株PTG的感染纳入分析。由于众所周知的TLR-MyD 88信号轴在人类中可能不太重要，我们检查了MyD 88 +/+和MyD 88 −/− BMDM的转录反应。长链非编码（lnc）RNA分子正在成为感染和免疫中的关键调节因子，因此被纳入我们的分析。我们发现更多的宿主基因差异表达的高毒力RH株，而不是与毒性较低的PTG株（335对74蛋白编码基因的RH和PTG，分别）。富含这些蛋白质编码基因的是与免疫应答以及细胞粘附和迁移相关的子集。我们确定了249和83个非编码RNA的差异表达在感染RH和PTG菌株，分别。尽管其中大部分功能未知，但一种名为mir 17 hg的保守lncRNA编码mir 17 microRNA基因簇，该基因簇与T.弓形虫感染MyD 88基因敲除细胞和野生型细胞之间只有极少量的转录本差异表达。然而，几个免疫基因的差异。而寄生虫分泌蛋白的转录本在T.在感染过程中的弓形虫基因，当比较MyD 88敲除和野生型宿主BMDM中的感染时，未鉴定出差异表达的寄生虫基因。本文提供的大数据集为继续研究MyD 88非依赖性免疫应答和lncRNA在弓形虫感染过程中的功能奠定了基础。在线版本包含补充材料，可通过10.1186/s12864-021-07437-0获得。
Toxoplasma gondii is a globally distributed protozoan parasite that establishes life-long asymptomatic infection in humans, often emerging as a life-threatening opportunistic pathogen during immunodeficiency. As an intracellular microbe, Toxoplasma establishes an intimate relationship with its host cell from the outset of infection. Macrophages are targets of infection and they are important in early innate immunity and possibly parasite dissemination throughout the host. Here, we employ an RNA-sequencing approach to identify host and parasite transcriptional responses during infection of mouse bone marrow-derived macrophages (BMDM). We incorporated into our analysis infection with the high virulence Type I RH strain and the low virulence Type II strain PTG. Because the well-known TLR-MyD88 signaling axis is likely of less importance in humans, we examined transcriptional responses in both MyD88+/+ and MyD88−/− BMDM. Long noncoding (lnc) RNA molecules are emerging as key regulators in infection and immunity, and were, therefore, included in our analysis. We found significantly more host genes were differentially expressed in response to the highly virulent RH strain rather than with the less virulent PTG strain (335 versus 74 protein coding genes for RH and PTG, respectively). Enriched in these protein coding genes were subsets associated with the immune response as well as cell adhesion and migration. We identified 249 and 83 non-coding RNAs as differentially expressed during infection with RH and PTG strains, respectively. Although the majority of these are of unknown function, one conserved lncRNA termed mir17hg encodes the mir17 microRNA gene cluster that has been implicated in down-regulating host cell apoptosis during T. gondii infection. Only a minimal number of transcripts were differentially expressed between MyD88 knockout and wild type cells. However, several immune genes were among the differences. While transcripts for parasite secretory proteins were amongst the most highly expressed T. gondii genes during infection, no differentially expressed parasite genes were identified when comparing infection in MyD88 knockout and wild type host BMDM. The large dataset presented here lays the groundwork for continued studies on both the MyD88-independent immune response and the function of lncRNAs during Toxoplasma gondii infection. The online version contains supplementary material available at 10.1186/s12864-021-07437-0.
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DOI：
10.4049/jimmunol.1501137
发表时间：
2015-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Cohen SB;Denkers EY
通讯作者：
Denkers EY
影响因子：
14.9
作者：
Frankish A;Diekhans M;Ferreira AM;Johnson R;Jungreis I;Loveland J;Mudge JM;Sisu C;Wright J;Armstrong J;Barnes I;Berry A;Bignell A;Carbonell Sala S;Chrast J;Cunningham F;Di Domenico T;Donaldson S;Fiddes IT;García Girón C;Gonzalez JM;Grego T;Hardy M;Hourlier T;Hunt T;Izuogu OG;Lagarde J;Martin FJ;Martínez L;Mohanan S;Muir P;Navarro FCP;Parker A;Pei B;Pozo F;Ruffier M;Schmitt BM;Stapleton E;Suner MM;Sycheva I;Uszczynska-Ratajczak B;Xu J;Yates A;Zerbino D;Zhang Y;Aken B;Choudhary JS;Gerstein M;Guigó R;Hubbard TJP;Kellis M;Paten B;Reymond A;Tress ML;Flicek P
通讯作者：
Flicek P
影响因子：
6.7
作者：
Cohen SB;Maurer KJ;Egan CE;Oghumu S;Satoskar AR;Denkers EY
通讯作者：
Denkers EY
巨噬细胞中弓形虫感染后 STAT3 依赖性 miRNA 基因反式激活
影响因子：
3.2
作者：
Cai Y;Chen H;Jin L;You Y;Shen J
通讯作者：
Shen J
影响因子：
29.7
作者：
Atianand MK;Caffrey DR;Fitzgerald KA
通讯作者：
Fitzgerald KA