Buchon Nicolas, Broderick Nichole A, Chakrabarti Sveta, Lemaitre Bruno
Global Health Institute, Ecole Polytechnique Federale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
Genes Dev. 2009 Oct 1;23(19):2333-44. doi: 10.1101/gad.1827009.
Gut homeostasis is controlled by both immune and developmental mechanisms, and its disruption can lead to inflammatory disorders or cancerous lesions of the intestine. While the impact of bacteria on the mucosal immune system is beginning to be precisely understood, little is known about the effects of bacteria on gut epithelium renewal. Here, we addressed how both infectious and indigenous bacteria modulate stem cell activity in Drosophila. We show that the increased epithelium renewal observed upon some bacterial infections is a consequence of the oxidative burst, a major defense of the Drosophila gut. Additionally, we provide evidence that the JAK-STAT (Janus kinase-signal transducers and activators of transcription) and JNK (c-Jun NH(2) terminal kinase) pathways are both required for bacteria-induced stem cell proliferation. Similarly, we demonstrate that indigenous gut microbiota activate the same, albeit reduced, program at basal levels. Altered control of gut microbiota in immune-deficient or aged flies correlates with increased epithelium renewal. Finally, we show that epithelium renewal is an essential component of Drosophila defense against oral bacterial infection. Altogether, these results indicate that gut homeostasis is achieved by a complex interregulation of the immune response, gut microbiota, and stem cell activity.
肠道稳态受免疫和发育机制的共同控制，其破坏可导致肠道炎症性疾病或癌变。虽然细菌对黏膜免疫系统的影响开始得到精确了解，但关于细菌对肠道上皮更新的影响却知之甚少。在此，我们探讨了感染性细菌和原生细菌如何调节果蝇的干细胞活性。我们发现，某些细菌感染后观察到的上皮更新增加是氧化爆发的结果，氧化爆发是果蝇肠道的主要防御机制。此外，我们提供证据表明，JAK-STAT（Janus激酶-信号转导子和转录激活子）和JNK（c-Jun氨基末端激酶）通路对于细菌诱导的干细胞增殖都是必需的。同样，我们证明原生肠道微生物群在基础水平上激活相同但程度较低的程序。免疫缺陷或老龄果蝇中肠道微生物群的控制改变与上皮更新增加相关。最后，我们表明上皮更新是果蝇抵抗口腔细菌感染防御的重要组成部分。总之，这些结果表明，肠道稳态是通过免疫反应、肠道微生物群和干细胞活性的复杂相互调节来实现的。
