Heat stress directly impairs gut integrity and recruits distinct immune cell populations into the bovine intestine
Heat stress directly impairs gut integrity and recruits distinct immune cell populations into the bovine intestine
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DOI：
10.1073/pnas.1820130116
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发表时间：
2019-05-21
影响因子：
11.1
通讯作者：
Kuehn, Christa
中科院分区：
文献类型：
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作者：
Koch, Franziska;Thom, Ulrike;Kuehn, Christa
高环境温度对生物体有多种潜在影响，如体温过高、内毒素血症和/或全身炎症。然而，通常很难区分表型效应的原因和后果，例如热应激通过减少食物摄入的间接影响。泌乳奶牛是一个特别敏感的模型，以检查热应激的影响，由于其密集的代谢产热和小的表面积：体积比。该模型的结果表明，热应激直接诱导了迄今未知的尚未分类的细胞浸润到空肠的粘膜和粘膜下层。由于成对饲喂设计，我们可以排除这种效应是同时发生的热诱导摄食量减少的结果。使用激光捕获显微切割和RNA测序的浸润细胞的分离和表征表明骨髓起源和巨噬细胞样表型。此外，靶向转录组分析提供了激活的免疫和吞噬相关途径的证据，LPS和细胞因子作为上游调节因子与热应激直接相关。最后，我们得到的迹象表明，热应激可能直接改变空肠紧密连接蛋白，表明受损的肠屏障。在热应激过程中，有毒和细菌化合物的渗透可能触发了调节的免疫库，并诱导了抗氧化防御机制，以维持肠道细菌和空肠免疫系统之间的稳态。我们的牛模型表明，在适度升高的环境温度下，热应激对哺乳动物空肠的直接影响。在开发对抗热应激负面影响的概念时，需要考虑这些结果。
High ambient temperature has multiple potential effects on the organism such as hyperthermia, endotoxemia, and/or systemic inflammation. However, it is often difficult to discriminate between cause and consequence of phenotypic effects, such as the indirect influence of heat stress via reduced food intake. Lactating dairy cows are a particularly sensitive model to examine the effects of heat stress due to their intensive metabolic heat production and small surface: volume ratio. Results from this model show heat stress directly induced a so-far unknown infiltration of yet uncategorized cells into the mucosa and submucosa of the jejunum. Due to a pair-feeding design, we can exclude this effect being a consequence of the concurrent heat-induced reduction in feed intake. Isolation and characterization of the infiltrating cells using laser capture microdissection and RNA sequencing indicated a myeloic origin and macrophage-like phenotype. Furthermore, targeted transcriptome analyses provided evidence of activated immune- and phagocytosis-related pathways with LPS and cytokines as upstream regulators directly associated with heat stress. Finally, we obtained indication that heat stress may directly alter jejunal tight junction proteins suggesting an impaired intestinal barrier. The penetration of toxic and bacterial compounds during heat stress may have triggered a modulated immune repertoire and induced an antioxidative defense mechanism to maintain homeostasis between commensal bacteria and the jejunal immune system. Our bovine model indicates direct effects of heat stress on the jejunum of mammals already at moderately elevated ambient temperature. These results need to be considered when developing concepts to combat the negative consequences of heat stress.