The DH31/CGRP enteroendocrine peptide triggers intestinal contractions favoring the elimination of opportunistic bacteria.
The DH31/CGRP enteroendocrine peptide triggers intestinal contractions favoring the elimination of opportunistic bacteria.
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DOI：
10.1371/journal.ppat.1007279
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发表时间：
2018-09
期刊：
影响因子：
6.7
通讯作者：
Gallet A
中科院分区：
文献类型：
--
作者：
Benguettat O;Jneid R;Soltys J;Loudhaief R;Brun-Barale A;Osman D;Gallet A
消化道是受食源性细菌摄入影响的第一个器官。当肠道细菌成为居民时，机会性或毒性细菌通过局部先天免疫系统从肠道中消除。在这里，我们描述了一种新的防御机制，独立的免疫系统，在果蝇。我们观察到强烈的收缩纵向内脏肌纤维的第一个2小时后细菌摄入。我们发现，这些内脏肌肉收缩是由免疫活性氧（ROS）引起的，这些活性氧在管腔中积累，并依赖于ROS敏感TRPA1受体。然后，我们证明，前肠内分泌细胞亚群需要ROS和TRPA 1来释放DH 31神经肽，从而激活邻近内脏肌肉中的受体。由此产生的内脏肌肉收缩有利于快速排出细菌，限制它们在肠道中的存在。我们的研究结果揭示了一个早熟的防御机制，对摄入的机会细菌，无论是革兰氏阳性如苏云金芽孢杆菌或革兰氏阴性如欧文氏菌carotovora carotovora。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。肠道是对抗与食物一起沿着摄入的非肠道细菌的第一道屏障。先天免疫系统是肠道内壁响应致病细菌以避免有害影响的主要手段。肠细胞产生氯漂白剂和抗菌肽，破坏外源性细菌。在这里，我们确定并表征了一种新的肠道防御机制，这种机制在摄入外源性细菌后迅速发生。我们发现，肠内分泌细胞通过传感器感知到管腔中氯漂白剂的存在。该传感器促进肠内分泌细胞内的钙流，从而允许激素的释放。这种激素通过引起肠道强烈收缩（或痉挛）局部作用于肠道周围的内脏肌肉。我们表明，这些强烈但短暂的内脏收缩有助于快速排出摄入的细菌，从而限制它们对肠道的潜在有害影响。显然，漂白传感器是众所周知的参与疼痛。因此，我们在这项研究中破译了一种迄今为止仅由医学经验描述的生物学机制，可能解释食物中毒后的肠道疼痛和内脏痉挛。
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. The intestine is the first barrier to fight non-commensal bacteria ingested along with the food. The innate immune system is the main mean mounted by the gut lining in response to ill-causing bacteria to avoid detrimental impact. Intestinal cells produce chlorine bleach and antimicrobial peptides that destroy exogenous bacteria. Here, we identified and characterized a new mechanism of gut defense that occurs rapidly after ingestion of exogenous bacteria. We found that the enteroendocrine cells perceive the presence of chlorine bleach in the lumen thanks to a sensor. This sensor promotes a calcium flux within enteroendocrine cells that allows the release of a hormone. This hormone acts locally on the visceral muscle surrounding the intestine by provoking its strong contractions (or spasms). We show that these strong but brief visceral contractions are helping to the quick expulsion of the ingested bacteria thus limiting their potential detrimental impact on the intestine. Markedly, the bleach-sensor is well known to be involved in pain. Therefore we have deciphered in this study a biological mechanism that has so far been described only empirically by medicine, potentially explaining intestinal pain and visceral spasms upon food poisoning.
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