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toll 途径以感染依赖的方式抑制组织生长并调节细胞适应性。

The Toll pathway inhibits tissue growth and regulates cell fitness in an infection-dependent manner.

机构信息

Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.

Institute of Cell Biology, University of Bern, Bern, Switzerland.

出版信息

Elife. 2018 Nov 19;7:e39939. doi: 10.7554/eLife.39939.

Abstract

The Toll pathway regulates the cellular response to infection via the transcriptional upregulation of antimicrobial peptides. In , apart from its role in innate immunity, this pathway has also been reported to be important for the elimination of loser cells in a process referred to as cell competition, which can be locally triggered by secreted factors released from winner cells. In this work, we provide evidence that the inhibition of Toll signaling not only increases the fitness of loser cells, but also bestows a clonal growth advantage on wild-type cells. We further demonstrate that this growth advantage depends on basal infection levels since it is no longer present under axenic conditions but exacerbated upon intense pathogen exposure. Thus, the Toll pathway functions as a fine-tuned pro-apoptotic and anti-proliferative regulator, underlining the existence of a trade-off between innate immunity and growth during development.

摘要

Toll 通路通过转录上调抗菌肽来调节细胞对感染的反应。在 中,除了在先天免疫中的作用外,该通路对于所谓的细胞竞争中失败者细胞的消除也很重要,细胞竞争可以通过来自胜利者细胞分泌的因子在局部触发。在这项工作中,我们提供的证据表明,Toll 信号的抑制不仅增加了失败者细胞的适应性,而且赋予了野生型细胞克隆生长优势。我们进一步证明,这种生长优势取决于基础感染水平,因为在无菌条件下不再存在,但在强烈的病原体暴露下加剧。因此,Toll 通路是一种精细的促凋亡和抗增殖调节剂,强调了在发育过程中先天免疫和生长之间存在权衡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df81/6279345/c4586646ad93/elife-39939-fig1.jpg

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