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The DH31/CGRP enteroendocrine peptide triggers intestinal contractions favoring the elimination of opportunistic bacteria

机译:DH31 / CGRP肠内分泌肽可触发肠道收缩有利于消除机会细菌

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摘要

The digestive tract is the first organ affected by the ingestion of foodborne bacteria. While commensal bacteria become resident, opportunistic or virulent bacteria are eliminated from the gut by the local innate immune system. Here we characterize a new mechanism of defense, independent of the immune system, in Drosophila melanogaster. We observed strong contractions of longitudinal visceral muscle fibers for the first 2 hours following bacterial ingestion. We showed that these visceral muscle contractions are induced by immune reactive oxygen species (ROS) that accumulate in the lumen and depend on the ROS-sensing TRPA1 receptor. We then demonstrate that both ROS and TRPA1 are required in a subset of anterior enteroendocrine cells for the release of the DH31 neuropeptide which activates its receptor in the neighboring visceral muscles. The resulting contractions of the visceral muscles favors quick expulsion of the bacteria, limiting their presence in the gut. Our results unveil a precocious mechanism of defense against ingested opportunistic bacteria, whether they are Gram-positive like Bacillus thuringiensis or Gram-negative like Erwinia carotovora carotovora. Finally, we found that the human homolog of DH31, CGRP, has a conserved function in Drosophila.
机译:消化道是第一个受食源性细菌影响的器官。当共生细菌成为常驻细菌时,局部先天免疫系统从肠道中消除了机会性细菌或强力细菌。在这里,我们描述了果蝇黑色素瘤的一种独立于免疫系统的新防御机制。在细菌摄入后的前两个小时,我们观察到纵向内脏肌纤维强烈收缩。我们表明,这些内脏肌肉收缩是由内腔中积累的并依赖于ROS感应TRPA1受体的免疫活性氧(ROS)诱导的。然后,我们证明在前肠内分泌细胞的一个子集中需要ROS和TRPA1释放DH31神经肽,从而激活其在邻近内脏肌肉中的受体。内脏肌肉的收缩有利于细菌的快速排出,从而限制了它们在肠道中的存在。我们的研究结果揭示了抵抗摄取的机会细菌的早熟机制,无论它们是苏云金芽孢杆菌(Bacillus thuringiensis)的革兰氏阳性菌,还是胡萝卜欧文氏菌(Erwinia carotovora carotovora)的革兰氏阴性菌。最后,我们发现DH31的人类同源物CGRP在果蝇中具有保守的功能。

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