The Invertebrate Lysozyme Effector ILYS-3 Is Systemically Activated in Response to Danger Signals and Confers Antimicrobial Protection in C. elegans.
The Invertebrate Lysozyme Effector ILYS-3 Is Systemically Activated in Response to Danger Signals and Confers Antimicrobial Protection in C. elegans.
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DOI：
10.1371/journal.ppat.1005826
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发表时间：
2016-08
期刊：
影响因子：
6.7
通讯作者：
Hodgkin J
中科院分区：
文献类型：
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作者：
Gravato-Nobre MJ;Vaz F;Filipe S;Chalmers R;Hodgkin J
关于线虫C中抗菌效应物的相对贡献和重要性知之甚少。尽管对这种生物体的先天免疫反应进行了大量的研究，本文研究了无脊椎动物型溶菌酶（ilys）基因的表达、功能和调控。优美的这些基因表现出令人惊讶的各种组织特异性表达模式和饥饿或细菌感染的反应。最强的表达，ilys-3，进行了详细的研究。ILYS-3蛋白在咽部和体腔细胞中组成型表达，在肠道中动态表达。对突变体的分析表明，ILYS-3是正常生长期间咽部研磨（破坏细菌细胞）所必需的，因此它有助于长寿，以及对细菌病原体的保护。饥饿和革兰氏阳性病原体的挑战导致肠中ILYS-3的ERK-MAPK依赖性上调。发现由病原体引起的肠道诱导，而不是饥饿，依赖于咽部而不是肠道中的MPK-1活性，表明这两种组织之间存在意想不到的交流。体腔细胞表达似乎对正常生长或免疫力贡献不大。发现重组ILYS-3蛋白对革兰氏阳性细胞壁材料表现出适当的裂解活性。针对细菌致病机制的天然免疫防御依赖于抗菌因子的激活。我们研究了一个基因家族的表达和相对重要性编码六个无脊椎动物型溶菌酶在线虫C。优雅的。ilys基因表现出不同的组织特异性表达模式和对病原性挑战和/或饥饿的反应。最丰富的表达，ilys-3，表现出组成性咽部表达，我们表明这是必要的有效破坏细菌在非致病性生长条件下，因此，它有助于正常的寿命。在饥饿或暴露于革兰氏阳性病原体（如嗜热微杆菌）后，ilys-3在肠细胞中也被强烈上调，并在限制肠感染的病原性损伤中充当“缓慢效应物”。我们发现，这种诱导病原体依赖于ERK-MAPK级联反应的行动，这在咽部，而不是肠细胞的行为，这意味着咽和肠之间的通信。标记的ILYS-3蛋白主要在饥饿后肠细胞的再循环内体和肠腔中检测到。ILYS-3也在体腔细胞（清道夫细胞）中表达，但我们发现这些细胞对防御几乎没有贡献。我们检测了重组ILYS-3蛋白的酶学性质，发现它具有抗M.紫茎泽兰细胞壁。
Little is known about the relative contributions and importance of antibacterial effectors in the nematode C. elegans, despite extensive work on the innate immune responses in this organism. We report an investigation of the expression, function and regulation of the six ilys (invertebrate-type lysozyme) genes of C. elegans. These genes exhibited a surprising variety of tissue-specific expression patterns and responses to starvation or bacterial infection. The most strongly expressed, ilys-3, was investigated in detail. ILYS-3 protein was expressed constitutively in the pharynx and coelomocytes, and dynamically in the intestine. Analysis of mutants showed that ILYS-3 was required for pharyngeal grinding (disruption of bacterial cells) during normal growth and consequently it contributes to longevity, as well as being protective against bacterial pathogens. Both starvation and challenge with Gram-positive pathogens resulted in ERK-MAPK-dependent up-regulation of ilys-3 in the intestine. The intestinal induction by pathogens, but not starvation, was found to be dependent on MPK-1 activity in the pharynx rather than in the intestine, demonstrating unexpected communication between these two tissues. The coelomocyte expression appeared to contribute little to normal growth or immunity. Recombinant ILYS-3 protein was found to exhibit appropriate lytic activity against Gram-positive cell wall material. Innate immune defenses against bacterial pathogenesis depend on the activation of antibacterial factors. We examined the expression and relative importance of a gene family encoding six invertebrate-type lysozymes in the much-studied nematode C. elegans. The ilys genes exhibit distinct patterns of tissue-specific expression and response to pathogenic challenge and/or starvation. The most abundantly expressed, ilys-3, exhibits constitutive pharyngeal expression, which we show is essential for efficient disruption of bacteria under non-pathogenic growth conditions, and consequently it contributes to normal longevity. ilys-3 is also strongly up-regulated in intestinal cells after starvation or exposure to Gram-positive pathogens such as Microbacterium nematophilum and acts as a ‘slow-effector’ in limiting pathogenic damage from intestinal infections. We show that this induction by pathogens depends on the action of an ERK-MAPK cascade, which acts in pharyngeal rather than intestinal cells; this implies communication between pharynx and intestine. Tagged ILYS-3 protein was detected mainly in recycling endosomes of intestinal cells and in the intestinal lumen after starvation. ILYS-3 was also expressed in coelomocytes (scavenger cells) but we found that these cells make little or no contribution to defense. We examined the enzymatic properties of recombinant ILYS-3 protein, finding that it has lytic activity against M. nematophilum cell-walls.