Caenorhabditis elegans are soil-dwelling nematodes and models for understanding innate immunity and infection. Previously, we developed a novel fluorescent dye (KR35) that accumulates in the intestine of C. elegans and reports a dynamic wave in intestinal pH associated with the defecation motor program. Here, we use KR35 to show that mutations in the Ca2+-binding protein, PBO-1, abrogate the pH wave, causing the anterior intestine to be constantly acidic. Surprisingly, pbo-1 mutants were also more susceptible to infection by several bacterial pathogens. We could suppress pathogen susceptibility in pbo-1 mutants by treating the animals with pH-buffering bicarbonate, suggesting the pathogen susceptibility is a function of the acidity of the intestinal pH. Furthermore, we use KR35 to show that upon infection by pathogens, the intestinal pH becomes neutral in a wild type, but less so in pbo-1 mutants. C. elegans is known to increase production of reactive oxygen species (ROS), such as H2O2, in response to pathogens, which is an important component of pathogen defense. We show that pbo-1 mutants exhibited decreased H2O2 in response to pathogens, which could also be partially restored in pbo-1 animals treated with bicarbonate. Ultimately, our results support a model whereby PBO-1 functions during infection to facilitate pH changes in the intestine that are protective to the host.

中文翻译：

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秀丽隐杆线虫CHP1同源物pbo-1通过调节肠腔的pH来发挥先天免疫功能。

秀丽隐杆线虫是居住在土壤中的线虫，是理解先天免疫和感染的模型。以前，我们开发了一种新型荧光染料（KR35），该染料在秀丽隐杆线虫的肠道中积累，并报告了与排便运动程序相关的肠道pH动态波。在这里，我们使用KR35来显示Ca2 +结合蛋白PBO-1中的突变消除了pH值波，从而导致前肠始终呈酸性。令人惊讶的是，pbo-1突变体也更容易受到几种细菌病原体的感染。我们可以通过用pH缓冲碳酸氢盐处理动物来抑制pbo-1突变体中的病原体敏感性，这表明病原体敏感性是肠道pH酸度的函数。此外，我们使用KR35来证明在被病原体感染后，在野生型中，肠道pH变为中性，而在pbo-1突变体中则不然。众所周知，秀丽隐杆线虫可响应病原体增加活性氧物种（ROS）（例如H2O2）的产生，而病原体是病原体防御的重要组成部分。我们表明pbo-1突变体表现出减少的H2O2响应病原体，这也可以在用碳酸氢盐处理过的pbo-1动物中部分恢复。最终，我们的结果支持了一种模型，在感染过程中PBO-1起作用以促进肠道中对宿主具有保护作用的pH值变化。我们表明pbo-1突变体表现出减少的H2O2响应病原体，这也可以在用碳酸氢盐处理过的pbo-1动物中部分恢复。最终，我们的结果支持了一种模型，在感染过程中PBO-1起作用以促进肠道中对宿主具有保护作用的pH值变化。我们显示pbo-1突变体表现出减少的H2O2响应病原体，这也可以在用碳酸氢盐处理过的pbo-1动物中部分恢复。最终，我们的结果支持了一个模型，在感染过程中PBO-1起作用以促进肠道中对宿主具有保护作用的pH值变化。