Identification and functional analysis of antifungal immune response genes in Drosophila.
Identification and functional analysis of antifungal immune response genes in Drosophila.
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DOI：
10.1371/journal.ppat.1000168
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发表时间：
2008-10-03
期刊：
影响因子：
6.7
通讯作者：
Kim YJ
中科院分区：
文献类型：
--
作者：
Jin LH;Shim J;Yoon JS;Kim B;Kim J;Kim-Ha J;Kim YJ
对微生物感染的先天免疫反应的基本方面似乎在昆虫和哺乳动物之间是保守的。虽然已经详细研究了在对各种微生物的先天免疫应答期间激活NF-κB的信号通路，但是控制对真菌感染的其他免疫应答的调节机制需要进一步研究。为了确定新的果蝇基因参与抗真菌免疫反应，我们选择了已知在SL 2细胞中由微生物细胞壁成分差异调节的基因，并使用突变果蝇测试了它们在抗真菌防御中的作用。从130个突变株系中，有16个突变株表现出对真菌感染的敏感性增加。对它们对防御各种类型的细菌和真菌的影响的研究揭示了9个基因，它们专门参与防御真菌感染。所有这些突变体显示缺陷的吞噬或激活的抗菌肽基因感染后。在一些突变体中，这些免疫缺陷归因于血细胞发育和分化的缺陷，而其他突变体在体液或细胞免疫应答所需的免疫信号传导中显示出特定缺陷。我们的研究结果确定了一类新的基因参与抗真菌免疫反应的果蝇。先天免疫反应是昆虫和哺乳动物抵抗微生物感染的第一道防线。在果蝇中，有助于先天免疫应答的多种防御机制包括抗菌肽（AMP）、活性氧、吞噬作用和黑化。对参与这些免疫过程的基因的研究发现了16种突变体，这些突变体在感染后表现出更高的致死率。这些基因的不同功能表明了防御真菌感染所需的调控机制的复杂性。谱系特异性转录因子和染色质修饰剂似乎是必要的功能性血细胞的正常发育，而细胞骨架调节剂需要血细胞的吞噬活性。此外，我们确定了几个基因参与AMP合成或黑化所需的免疫信号。这些结果可能为定义一类新的参与体液和细胞抗真菌免疫应答的基因奠定基础。
Essential aspects of the innate immune response to microbial infection appear to be conserved between insects and mammals. Although signaling pathways that activate NF-κB during innate immune responses to various microorganisms have been studied in detail, regulatory mechanisms that control other immune responses to fungal infection require further investigation. To identify new Drosophila genes involved in antifungal immune responses, we selected genes known to be differentially regulated in SL2 cells by microbial cell wall components and tested their roles in antifungal defense using mutant flies. From 130 mutant lines, sixteen mutants exhibited increased sensitivity to fungal infection. Examination of their effects on defense against various types of bacteria and fungi revealed nine genes that are involved specifically in defense against fungal infection. All of these mutants displayed defects in phagocytosis or activation of antimicrobial peptide genes following infection. In some mutants, these immune deficiencies were attributed to defects in hemocyte development and differentiation, while other mutants showed specific defects in immune signaling required for humoral or cellular immune responses. Our results identify a new class of genes involved in antifungal immune responses in Drosophila. The innate immune response is the first line of defense against microbial infections in insects and mammals. In Drosophila, multiple defense mechanisms that contribute to the innate immune response include antimicrobial peptides (AMP), reactive oxygen species, phagocytosis and melanization. A search for genes involved in these immune processes identified sixteen mutants that exhibited increased lethality after infection. The diverse functions annotated to these genes indicate the complexity of the regulatory mechanisms required for defense against fungal infection. Lineage specific transcription factors and chromatin modifiers appeared to be required for proper development of functional hemocytes, while cytoskeletal regulators were required for phagocytotic activities of hemocytes. In addition, we identified several genes involved in the immune signaling required for AMP synthesis or melanization. These results may lay the foundation for defining a new class of genes that are involved in humoral and cellular antifungal immune responses.
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