Researchers at the University of Connecticut School of Medicine have described how the sympathetic nervous system plays a role in controlling antitumor immunity. The sympathetic nervous system innervates the lymph nodes, and immune cells have receptors that allow them to directly sense adrenaline signaling. In their work, the researchers showed that if sympathetic signaling was disrupted, it prevented the proper development of myeloid cells in both normal and tumor-bearing mice. The accumulation of immature myeloid-derived suppressor cells in turn increased the number of regulatory T cells, further contributing to reduced antitumor immunity. The authors concluded that “our results describe a regulatory framework in which sympathetic tone controls the development of innate and adaptive immune cells and influences their activity in health and disease.” They reported their findings in the Sept. 11, 2020, issue of Science Immunology.
Killing persisters with less toxicity
By using combinations of strongly and weakly metabolism-dependent antibiotics, researchers at the Massachusetts Institute of Technology have eradicated persister bacteria. Such persisters are distinct from drug-resistant bacteria because they evade the effects of antibiotics by slowing down their metabolism. Persisters are major contributors to chronic infections, and antibiotics that are only weakly dependent on target cell metabolism – including the antibiotic of last resort colistin – have high toxicity to human cells. In their work, the authors first identified the extent to which different antibiotics were dependent on an active target cell metabolism to work. They then showed that combining antibiotics with high and low metabolic dependence could “sterilize bacterial cultures, including persister cells, while reducing the amount of toxic antibiotics required,” they wrote. “This work demonstrates the utility of a metabolism-focused approach to antibiotic therapy that accounts for the heterogeneity present in bacterial cultures.” They reported their results in the Sept. 10, 2020, issue of Cell Chemical Biology.