Multiple pals gene modules control a balance between immunity and development in Caenorhabditis elegans.
Multiple pals gene modules control a balance between immunity and development in Caenorhabditis elegans.
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多个 pals 基因模块控制着秀丽隐杆线虫免疫和发育之间的平衡。
DOI：
10.1101/2023.01.15.524171
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Troemel,EmilyR
中科院分区：
文献类型：
--
作者：
Lažetić,Vladimir;Blanchard,MichaelJ;Bui,Theresa;Troemel,EmilyR
免疫系统不断与病原体诱导的压力作斗争，这通常导致免疫基因家族以物种特异性方式进化扩张。例如，在秀丽隐杆线虫基因组中，palsgene家族扩大到39个成员，而不是单一的线虫palsortholog。我们以前的研究表明，该家族的两个成员，帕尔斯-22和帕尔斯-25，作为拮抗性旁系同源物控制胞内病原体反应（IPR）。IPR是一种保护性转录反应，在感染两种分子上不同的秀丽隐杆线虫细胞内病原体--来自微孢子虫门的奥赛病毒和杀线虫真菌时被激活。在这项研究中，我们确定了一个以前未被鉴定的pals家族成员，帕尔斯-17，作为一个新描述的IPR的负调控因子。帕尔斯-17突变体显示IPR基因表达的组成性上调，对细胞内病原体的免疫力增强，以及发育和生殖受损。我们还发现另外两个以前未被鉴定的pals基因，帕尔斯-20和帕尔斯-16，是IPR的正调控因子，作用于帕尔斯-17的下游。这些正调控因子逆转了pals-17缺失对IPR基因表达、免疫和发育的影响。我们发现，IPR负调节蛋白帕尔斯-17和IPR正调节蛋白帕尔斯-20共定位于肠上皮细胞内和顶端侧，这是IPR诱导病原体感染的部位。总之，我们的研究表明，几个palsgenes从expandedpalsgenes家族作为开/关开关模块，以调节生物体发育和免疫力之间的平衡，对自然细胞内病原体在秀丽隐杆线虫。
The immune system continually battles against pathogen-induced pressures, which often leads to the evolutionary expansion of immune gene families in a species-specific manner. For example, thepalsgene family expanded to 39 members in theCaenorhabditis elegansgenome, in comparison to a single mammalianpalsortholog. Our previous studies have revealed that two members of this family,pals-22andpals-25, act as antagonistic paralogs to control the Intracellular Pathogen Response (IPR). The IPR is a protective transcriptional response, which is activated upon infection by two molecularly distinct natural intracellular pathogens ofC.elegans–the Orsay virus and the fungusNematocida parisiifrom the microsporidia phylum. In this study, we identify a previously uncharacterized member of thepalsfamily,pals-17, as a newly described negative regulator of the IPR.pals-17mutants show constitutive upregulation of IPR gene expression, increased immunity against intracellular pathogens, as well as impaired development and reproduction. We also find that two other previously uncharacterizedpalsgenes,pals-20andpals-16, are positive regulators of the IPR, acting downstream ofpals-17. These positive regulators reverse the effects caused by the loss ofpals-17on IPR gene expression, immunity, and development. We show that the negative IPR regulator protein PALS-17 and the positive IPR regulator protein PALS-20 colocalize inside and at the apical side of intestinal epithelial cells, which are the sites of infection for IPR-inducing pathogens. In summary, our study demonstrates that severalpalsgenes from the expandedpalsgene family act as ON/OFF switch modules to regulate a balance between organismal development and immunity against natural intracellular pathogens inC.elegans.