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在感染过程中,脂肪体中 IMD、Toll 和 Jak/STAT 免疫途径基因的调控。

Modulation of IMD, Toll, and Jak/STAT Immune Pathways Genes in the Fat Body of During Infection.

机构信息

Centro de Bioinvestigaciones (CeBio), Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires (CIT-NOBA), Universidad Nacional del Noroeste de la Provincia de Buenos Aires (UNNOBA)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Pergamino, Argentina.

Vector Behaviour and Pathogen Interaction Group, Instituto René Rachou, Fundação Oswaldo Cruz (FIOCRUZ), Belo Horizonte, Brazil.

出版信息

Front Cell Infect Microbiol. 2021 Jan 18;10:598526. doi: 10.3389/fcimb.2020.598526. eCollection 2020.

Abstract

is the second most common American trypanosome that infects man. It is vectored by triatomines from the genus , in which it invades the hemolymph and infects the salivary glands, avoiding the bug immune responses. In insects, these responses are initiated by well conserved pathways, mainly the IMD, Toll, and Jak/STAT. We hypothesize that long-term infection with in the gut or hemolymph of triggers different systemic immune responses, which influence the number of parasites that survive inside the vector. Thus, we investigated groups of insects with infections in the gut and/or hemolymph, and evaluated the parasite load and the expression in the fat body of transcription factors (, , and ) and inhibitors ( and ) of the IMD, Toll, and Jak/STAT pathways. We detected lower parasite counts in the gut of insects without hemolymph infection, compared to hemolymph-infected groups. Besides, we measured higher parasite numbers in the gut of bugs that were first inoculated with and then fed on infected mice, compared with control insects, indicating that hemolymph infection increases parasite numbers in the gut. Interestingly, we observed that genes from the three immune pathways where differentially modulated, depending on the region parasites were present, as we found (1) downregulated in gut-and/or-hemolymph-infected insects, compared with controls; (2) upregulated in gut-infected insect, compared with controls and gut-and-hemolymph-infected groups; and (3) downregulated in all groups of hemolymph-infected insects. Finally, we uncovered negative correlations between parasite loads in the gut and and expression, and between parasite counts in the hemolymph and levels, suggesting an association between parasite numbers and the IMD and Toll pathways. Overall, our findings reveal new players in - interactions that could be key for the capacity of the bug to transmit the pathogen.

摘要

是感染人类的第二大常见美洲锥虫。它由 属的三锥虫传播,在三锥虫中,它入侵血淋巴并感染唾液腺,从而避免了虫子的免疫反应。在昆虫中,这些反应是由高度保守的途径引发的,主要是 IMD、Toll 和 Jak/STAT。我们假设,在 肠道或血淋巴中长期感染 会引发不同的全身免疫反应,从而影响在载体中存活的寄生虫数量。因此,我们研究了肠道和/或血淋巴感染的昆虫群体,并评估了脂肪体中转录因子( 、 、 )和 IMD、Toll 和 Jak/STAT 途径抑制剂( 、 )的寄生虫负荷和表达。我们发现,与血淋巴感染组相比,没有血淋巴感染的昆虫肠道中的寄生虫数量较少。此外,我们测量了先接种 然后喂食感染小鼠的昆虫肠道中更高的寄生虫数量,与对照昆虫相比,这表明血淋巴感染会增加肠道中的寄生虫数量。有趣的是,我们观察到,三种免疫途径的基因根据寄生虫存在的区域而不同程度地被调节,我们发现(1)与对照组相比,在肠道和/或血淋巴感染的昆虫中下调;(2)在肠道感染的昆虫中上调,与对照组和肠道和血淋巴感染组相比;(3)在所有血淋巴感染组的昆虫中下调。最后,我们发现肠道中寄生虫负荷与 和 表达之间以及血淋巴中寄生虫计数与 水平之间呈负相关,表明寄生虫数量与 IMD 和 Toll 途径之间存在关联。总的来说,我们的发现揭示了 - 相互作用中的新参与者,这些参与者可能是虫子传播病原体的能力的关键。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be1e/7848085/a8851eec9019/fcimb-10-598526-g001.jpg

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