An innate immune response of blood cells to tumors and tissue damage in Drosophila
An innate immune response of blood cells to tumors and tissue damage in Drosophila
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DOI：
10.1242/dmm.000950
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发表时间：
2008-09-01
影响因子：
4.3
通讯作者：
Xu, Tian
中科院分区：
文献类型：
--
作者：
Pastor-Pareja, Jose Carlos;Wu, Ming;Xu, Tian
在老鼠和人类身上的研究已经证明了免疫系统在防止肿瘤生长方面的作用。破译肿瘤免疫反应的机制对于我们理解免疫识别和癌症进展是至关重要的。在这里，我们报告了果蝇对肿瘤的先天免疫反应。我们发现，当检测到基底膜破裂时，循环中的血细胞，称为血细胞，附着在肿瘤上，并随后阻止它们的生长。基底膜成分在整个动物界都非常保守，为免疫系统提供了一种独特的结构来感知组织的完整性。此外，我们发现，组织损伤激活了肿瘤和无菌伤口中的JNK信号，导致JAK/STAT激活细胞因子的表达。损伤组织的细胞因子分泌通过诱导血细胞和脂肪体中额外的细胞因子表达而放大为全身反应，从而导致血细胞增殖。我们的发现揭示了苍蝇对肿瘤和伤口的常见反应机制。类似的先天反应可能是脊椎动物和人类对肿瘤和组织损伤的反应基础。
Studies in mice and humans have demonstrated a role for the immune system in preventing the growth of tumors. Deciphering the mechanisms involved in the immune response to tumors is essential to our understanding of immune recognition and cancer progression. Here we report an innate immune response to tumors in Drosophila melanogaster. We found that circulating blood cells, termed hemocytes, adhere to tumors upon detection of basement membrane disruption, and subsequently counter their growth. Basement membrane components are remarkably conserved throughout the animal kingdom, providing a unique structure for the immune system to sense tissue integrity. Further, we show that tissue damage activates JNK signaling in both tumors and aseptic wounds, causing expression of JAK/STAT-activating cytokines. Cytokine secretion from the injured tissue is amplified into a systemic response through the induction of additional cytokine expression in the hemocytes and the fat body, resulting in hemocyte proliferation. Our findings reveal common mechanisms in the response to tumors and wounds in flies. A similar innate reaction may underlie the response to tumors and tissue damage in vertebrates and humans.