Combined Cellular Thermometry Reveals That Salmonella typhimurium Warms Macrophages by Inducing a Pyroptosis-like Phenotype.
Combined Cellular Thermometry Reveals That Salmonella typhimurium Warms Macrophages by Inducing a Pyroptosis-like Phenotype.
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DOI：
10.1021/jacs.2c07287
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发表时间：
2022-10
影响因子：
15
通讯作者：
Leyang Wu;F. Chen;Xiaoyao Chang;Lin Li;Xingpeng Yin;Can Li;Fangxu Wang;Chenyang Li;Qin Xu;Hongqin Zhuang;Ning Gu;Z. Hua
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文献类型：
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作者：
Leyang Wu;F. Chen;Xiaoyao Chang;Lin Li;Xingpeng Yin;Can Li;Fangxu Wang;Chenyang Li;Qin Xu;Hongqin Zhuang;Ning Gu;Z. Hua
减毒鼠伤寒沙门氏菌VNP20009富含肿瘤，已知具有抗肿瘤作用并招募巨噬细胞。然而，关于VNP是否会导致巨噬细胞的特定变化，例如细胞温度，人们知之甚少。在这里，使用实时无线多细胞测温系统，我们首次报告了VNP20009使巨噬细胞温度增加0.2°C。尼日利亚被认为是软下垂的诱导剂，被发现能诱导巨噬细胞升温。此外，ΔSIPD-VNP20009株不能诱导巨噬细胞下垂，同时也不能使巨噬细胞升温，不能引起下垂的GSDMD-/-巨噬细胞在VNP20009诱导后不再加温。这些结果提示巨噬细胞下垂的发生是VNP20009介导的细胞升温的关键。在单细胞测温系统的帮助下，进一步证实了细胞升温发生在松果体症样巨噬细胞中。在线粒体生物学功能丧失的巨噬细胞中，在诱导下垂后未检测到细胞升温，提示线粒体在升温中起着关键作用。此外，我们还发现VNP20009引起局部肿瘤温度升高。巨噬细胞清除后，VNP20009对肿瘤局部的增温作用明显减弱。值得注意的是，这种温度升高导致了M1型偏振。这些发现扩大了我们对该菌株引起的巨噬细胞的细胞生物学变化以及伴随着下睑下垂的生化现象的了解，并为利用联合细胞级温度检测器将生化信号转换为生物温度信号的研究提供了参考。
The attenuated Salmonella typhimurium VNP20009, enriched in tumors, is known to have antitumor effects and recruit macrophages. Little is known, however, about whether VNP will lead to specific changes in macrophages, e.g., cell temperature. Here, using a real-time wireless multicell thermometry system, we reported for the first time that VNP20009 increases the macrophage temperature by 0.2 °C. Nigericin, recognized as an inducer of pyroptosis, was found to induce macrophage warming. Moreover, the ΔsipD-VNP20009 strain failed to induce macrophage pyroptosis and simultaneously failed to warm macrophages, and the Gsdmd-/- macrophages that were unable to achieve pyroptosis were no longer warmed following VNP20009 induction. These results suggested that the occurrence of macrophage pyroptosis is the key to VNP20009-mediated cell warming. With the aid of a single-cell thermometry system, it was further confirmed that cell warming occurred in pyroptosis-like macrophages. Cellular warming was not detected after the induction of pyroptosis in macrophages with loss of mitochondrial biological function, suggesting a critical role of mitochondria in warming. Moreover, we found that VNP20009 caused local tumor temperature increases. The local tumor warming induced by VNP20009 was significantly reduced after macrophage clearance. Notably, this temperature increase contributed to M1-type polarization. These findings expanded our knowledge of the cellular biological changes induced by the strain on macrophages, as well as the biochemical phenomena accompanying pyroptosis, and provide a reference for the study of biochemical signals transduced to biothermal signals with a combined cell-level temperature detector.