Trypanosoma brucei triggers a broad immune response in the adipose tissue.
Trypanosoma brucei triggers a broad immune response in the adipose tissue.
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布氏锥虫在脂肪组织中引发广泛的免疫反应。
DOI：
10.1371/journal.ppat.1009933
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发表时间：
2021-09
期刊：
影响因子：
6.7
通讯作者：
Figueiredo LM
中科院分区：
文献类型：
--
作者：
Machado H;Bizarra-Rebelo T;Costa-Sequeira M;Trindade S;Carvalho T;Rijo-Ferreira F;Rentroia-Pacheco B;Serre K;Figueiredo LM
脂肪组织是布氏锥虫的主要宿主之一，布氏锥虫是昏睡病的病原体，昏睡病是人类的一种致命疾病。在小鼠中，性腺脂肪组织（AT）通常含有200万至500万寄生虫，而大多数实体器官显示寄生虫少10至100倍。在这项研究中，我们测试了AT环境是否对寄生虫的存在产生免疫反应。T.布鲁氏菌感染的脂肪组织揭示了大多数上调的宿主基因涉及炎症和免疫细胞功能。组织化学和流式细胞术证实感染后浸润的巨噬细胞、中性粒细胞和CD 4+和CD 8 + T淋巴细胞的数量越来越多。这些淋巴细胞中的大部分有效地产生1型效应细胞因子IFN-γ和TNF-α。此外，随着感染的进展，脂肪组织显示抗原特异性IgM和IgG抗体的积累。缺乏T和/或B细胞（Rag 2-/-、Jht-/-）或特征性细胞因子（Ifng-/-）的小鼠在循环和AT中均显示出较高的寄生虫负荷，证明了适应性免疫系统在两个区室中的关键作用。有趣的是，C3-/-小鼠的感染表明，虽然补体系统是控制血液中的寄生虫负荷，但它在AT和其他实体组织中是必要的。我们的结论是T.布氏杆菌感染在AT中触发广泛和强有力的免疫应答，这需要补体系统局部减少寄生虫负荷。非洲锥虫病是一种被忽视的疾病，在撒哈拉以南非洲造成重大社会经济负担。原生动物寄生虫布氏锥虫是非洲锥虫病的病原体，可在受感染宿主的血液和血管外空间中发现。不知什么原因，T。布鲁氏菌以非常高的数量在脂肪组织（AT）中积累。在这里，我们使用了多学科的方法来评估是否在T。布氏杆菌感染我们发现，随着感染的进展，各种各样的免疫细胞和抗体在AT中积累。我们还发现，这种广泛的免疫反应部分能够控制AT中的寄生虫数量。本研究为T.存在于AT中的布鲁氏菌寄生虫受到免疫监视。T.布氏杆菌在AT中如此高程度的积累仍有待阐明。
Adipose tissue is one of the major reservoirs of Trypanosoma brucei parasites, the causative agent of sleeping sickness, a fatal disease in humans. In mice, the gonadal adipose tissue (AT) typically harbors 2–5 million parasites, while most solid organs show 10 to 100-fold fewer parasites. In this study, we tested whether the AT environment responds immunologically to the presence of the parasite. Transcriptome analysis of T. brucei infected adipose tissue revealed that most upregulated host genes are involved in inflammation and immune cell functions. Histochemistry and flow cytometry confirmed an increasingly higher number of infiltrated macrophages, neutrophils and CD4+ and CD8+ T lymphocytes upon infection. A large proportion of these lymphocytes effectively produce the type 1 effector cytokines, IFN-γ and TNF-α. Additionally, the adipose tissue showed accumulation of antigen-specific IgM and IgG antibodies as infection progressed. Mice lacking T and/or B cells (Rag2-/-, Jht-/-), or the signature cytokine (Ifng-/-) displayed a higher parasite load both in circulation and in the AT, demonstrating the key role of the adaptive immune system in both compartments. Interestingly, infections of C3-/- mice showed that while complement system is dispensable to control parasite load in the blood, it is necessary in the AT and other solid tissues. We conclude that T. brucei infection triggers a broad and robust immune response in the AT, which requires the complement system to locally reduce parasite burden. African trypanosomiasis is a neglected disease with significant socio-economic burden in sub-Saharan Africa. The protozoan parasite Trypanosoma brucei, a causative agent of African trypanosomiasis, can be found in the blood and extra-vascular spaces of the infected host. For an unknown reason, T. brucei accumulates in adipose tissue (AT) in very high numbers. Here we used a multidisciplinary approach to assess whether an immune response was mounted in AT during a T. brucei infection. We found that as infection progresses, a broad variety of immune cells and antibodies accumulate in the AT. We also found that this broad immune response is partially able to control parasite numbers in the AT. Our study provides evidence that T. brucei parasites present in the AT are subjected to immune surveillance. The reason why T. brucei accumulates to such a high extent in AT remains to be elucidated.
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