Trypanosoma brucei Parasites Occupy and Functionally Adapt to the Adipose Tissue in Mice.
Trypanosoma brucei Parasites Occupy and Functionally Adapt to the Adipose Tissue in Mice.
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DOI：
10.1016/j.chom.2016.05.002
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发表时间：
2016-06-08
影响因子：
30.3
通讯作者：
Figueiredo LM
中科院分区：
文献类型：
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作者：
Trindade S;Rijo-Ferreira F;Carvalho T;Pinto-Neves D;Guegan F;Aresta-Branco F;Bento F;Young SA;Pinto A;Van Den Abbeele J;Ribeiro RM;Dias S;Smith TK;Figueiredo LM
布氏锥虫是一种引起昏睡病的细胞外寄生虫。在哺乳动物宿主中，锥虫被认为存在于两个主要的小生境中：感染早期，它们在血液中繁殖;后来，它们突破血脑屏障。通过对一个成熟的小鼠模型的研究，我们发现脂肪组织构成了布氏锥虫的第三个主要宿主。来自脂肪组织的寄生虫，在此称为脂肪组织形式（ATF），可以复制并且能够感染未感染动物。ATF在转录上与血流形式不同，上调的基因包括推定的脂肪酸β-氧化酶。与此一致，ATF能够利用外源肉豆蔻酸并形成β-氧化中间体，表明ATF寄生虫可以使用脂肪酸作为外部碳源。这些发现将脂肪组织确定为布氏锥虫在其哺乳动物生命周期中的生态位，并可能解释与昏睡病相关的体重减轻。布氏锥虫在小鼠感染后早期在脂肪组织中积累脂肪组织形式（ATF）可以复制并能够感染幼稚小鼠ATF在转录上是不同的并且上调脂肪酸代谢基因ATF可以主动摄取外源性肉豆蔻酸并形成β-氧化中间体布氏锥虫在哺乳动物宿主的血流和几个器官的间质区室中发现。特林达德等人发现脂肪组织是主要的血管外寄生虫生态位。在这种富含脂质的环境中，寄生虫基因表达的广泛重塑包括脂肪酸β-氧化酶的上调，这表明了功能性适应。
Trypanosoma brucei is an extracellular parasite that causes sleeping sickness. In mammalian hosts, trypanosomes are thought to exist in two major niches: early in infection, they populate the blood; later, they breach the blood-brain barrier. Working with a well-established mouse model, we discovered that adipose tissue constitutes a third major reservoir for T. brucei. Parasites from adipose tissue, here termed adipose tissue forms (ATFs), can replicate and were capable of infecting a naive animal. ATFs were transcriptionally distinct from bloodstream forms, and the genes upregulated included putative fatty acid β-oxidation enzymes. Consistent with this, ATFs were able to utilize exogenous myristate and form β-oxidation intermediates, suggesting that ATF parasites can use fatty acids as an external carbon source. These findings identify the adipose tissue as a niche for T. brucei during its mammalian life cycle and could potentially explain the weight loss associated with sleeping sickness. T. brucei parasites accumulate in the adipose tissue early after mouse infection Adipose tissue forms (ATFs) can replicate and are capable of infecting naive mice ATFs are transcriptionally distinct and upregulate genes for fatty acid metabolism ATFs can actively uptake exogenous myristate and form β-oxidation intermediates Trypanosoma brucei is found in the bloodstream and interstitial compartment of several organs in the mammalian host. Trindade et al. uncover the adipose tissue as a major extravascular parasite niche. Extensive remodeling of parasite gene expression in this lipid-rich environment includes upregulation of fatty acid β-oxidation enzymes, suggestive of a functional adaptation.