Department of Medicine, Division of Hematology, University of Utah, Salt Lake City, United States.
Molecular Medicine Program, University of Utah, Salt Lake City, United States.
Elife. 2019 Sep 18;8:e44674. doi: 10.7554/eLife.44674.
Iron is essential for survival of most organisms. All organisms have thus developed mechanisms to sense, acquire and sequester iron. In s, iron uptake and sequestration are regulated by HIF-1. We previously showed that mutants are developmentally delayed when grown under iron limitation. Here we identify , encoding a nuclear receptor, in a screen conducted for mutations that rescue the developmental delay of mutants under iron limitation. loss upregulates the intestinal metal transporter SMF-3 to increase iron uptake in mutants. mutants display increased expression of innate immune genes and DAF-16/FoxO-Class II genes, and enhanced resistance to . These responses are dependent on the transcription factor PQM-1, which localizes to intestinal cell nuclei in mutants. Our data reveal how utilizes nuclear receptors to regulate innate immunity and iron availability, and show iron sequestration as a component of the innate immune response.
铁是大多数生物生存所必需的。因此，所有生物都发展出了感知、获取和隔离铁的机制。在真核生物中，铁的摄取和隔离受 HIF-1 调节。我们之前曾表明，在缺铁条件下生长时， 突变体的发育会延迟。在这里，我们在筛选可挽救缺铁条件下 突变体发育迟缓的突变体时，鉴定到编码核受体的 。 缺失会上调肠道金属转运蛋白 SMF-3，以增加 突变体中的铁摄取。 突变体显示出先天免疫基因和 DAF-16/FoxO-类 II 基因的表达增加，并增强对 的抗性。这些反应依赖于转录因子 PQM-1，它在 突变体的肠道细胞核中定位。我们的数据揭示了 如何利用核受体来调节先天免疫和铁的可用性，并显示铁隔离是先天免疫反应的一个组成部分。
