Combined Cellular Thermometry Reveals That Salmonella typhimurium Warms Macrophages by Inducing a Pyroptosis-like Phenotype

Abstract

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.

NIR-II Responsive Nanohybrids Incorporating Thermosensitive Hydrogel as Sprayable Dressing for Multidrug-Resistant-Bacteria Infected Wound Management

“…Compared to the ILGA group, the higher M2 polarization of macrophages in the groups of ILGA + NIR and ILGA@Gel + NIR might be ascribed to the NIR-induced PTT effect (Figure S25). − Meanwhile, the proportion of M1-type macrophages also decreased after being handled with ILGA@Gel + NIR (Figure d). To investigate whether M1-type macrophages could be transformed into the M2-type, the RAW264.7 cells were first induced to the M1 phenotype by LPS and then treated with ILGA@Gel + NIR.…”

Thermoelectric Nanofluidics Probing Thermal Heterogeneity inside Single Cells

“…Transient temperature fluctuations over a few seconds were also observed (see the inset in Figure b), which can be ascribed to dynamic activities in cells. Such a fine pattern of cellular temperature fluctuations has not been observed in fluorescent thermometry. , Compared with temperature profiles recorded with thermocouples, , better thermal and spatiotemporal features were obtained in this case, in which temperature variations in unstimulated cells can be studied.…”

“…Such a fine pattern of cellular temperature fluctuations has not been observed in fluorescent thermometry. 53,54 Compared with temperature profiles re-corded with thermocouples, 16,55 better thermal and spatiotemporal features were obtained in this case, in which temperature variations in unstimulated cells can be studied.…”

Engineered Enzyme-Loaded Erythrocyte Vesicles Precisely Deprive Tumoral Nutrients to Induce Synergistic Near-Infrared-II Photothermal Therapy and Immune Activation

“…After being incubated with EV@RGT-S, the M2-type macrophages decreased to 15.6%, and the M1-type macrophages increased to 36.4%. Additionally, light irradiation could further promote the polarization of the macrophage, which might be due to the heat effect . After treatments, the M2-type macrophage-associated genes, transforming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF), were significantly down-regulated, and the M1-type macrophage-related genes (TNF-α and IL-6) were up-regulated correspondingly (Figure G).…”

“…Additionally, light irradiation could further promote the polarization of the macrophage, which might be due to the heat effect. 34 After treatments, the M2-type macrophage-associated genes, trans- forming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF), were significantly down-regulated, and the M1-type macrophage-related genes (TNF-α and IL-6) were up-regulated correspondingly (Figure 4G). As M1-type macrophages could directly kill tumor cells by secreting toxic factors, macrophages with different treatments were further coincubated with MDA-MB-231 cells (Figure 4H).…”