Sepsis is associated with bacterial invasion and inflammation and has a high mortality rate. Previous studies have demonstrated that tripartite motif 59 (TRIM59) was involved in NF-κB signaling and could promote phagocytosis of macrophages, but the role of TRIM59 in sepsis is still unknown. In our study, we found that TRIM59 was downregulated in lipopolysaccharide (LPS)-stimulated bone marrow-derived macrophages (BMDMs). In the cecal ligation and puncture (CLP) sepsis mice model, the mortality of Trim59^flox/floxLyz-Cre (Trim59-cKO) mice was higher, the immune cell infiltration and damage of liver and lung were more severe, and bacteria burden was increased. We also found that TRIM59 altered the production of pro-inflammation cytokines, as well as macrophage phagocytosis ability. Further analysis indicated that NF-κB signal pathway and Fcγ receptors might be involved in these regulations. Our study demonstrated for the first time that TRIM59 protects mice from sepsis by regulating inflammation and phagocytosis in macrophages.

A number of studies have been carried out to investigate the association of X-ray repair complementing defective repair in Chinese hamster cells 6 (XRCC6) polymorphisms and cancer risks, and the results remained inconsistent and inconclusive.To assess the effect of XRCC6 polymorphisms on cancer susceptibility, we conducted a meta-analysis, up to May 23rd 2014, 6267 cases with different types of tumor and 7536 controls from 20 published case-control studies. Summary odds ratios and corresponding 95% confidence intervals for XRCC6 polymorphism and cancer risk were estimated using fixed- or random-effects models when appropriate. Heterogeneity was assessed by chi-squared-based Q-statistic test, and the sources of heterogeneity were explored by subgroup analyses, logistic meta-regression analyses and Galbraith plot. Publication bias was evaluated by Begg funnel plot and Egger test. Sensitivity analyses were also performed.The rs2267437 polymorphism was associated with a significant increase in risks of overall cancers, breast cancer, renal cell carcinoma and hepatocellular carcinoma, and it could increase the cancer risk in Asian population; the rs5751129 polymorphism could increase the cancer risk in overall cancers; the rs132770 polymorphism was associated with the increased renal cell carcinoma risk; furthermore, the rs132793 polymorphism could decrease breast cancer risk and increase risks in "other cancers".Overall, the results provided evidences that the single nucleotide polymorphisms in XRCC6 promoter region might play different roles in various cancers, indicating different cancers have different tumorigenesis mechanisms. Our studies may perhaps supplement for the disease monitoring of cancers in the future, and additional studies to determine the exact molecular mechanism might provide us with interventions to protect the susceptible subgroups.

Memory is no longer a privilege of adaptive immunity. Innate immune cells can exhibit a long-term immune activation after infection or vaccination, which is called “trained immunity.” In addition to defense against mycobacterial infection, BCG-induced trained immunity can also exert nonspecific protection, which is regulated by metabolic rewiring and epigenetic reprograming. Enhanced glycolysis and glutamine-driven tricarboxylic acid cycle have been proven to be important metabolic pathways for trained immunity induced by BCG, which is dependent on Akt/mTOR pathway.

More and more exosome-based therapeutics are being developed with advances in nanotechnology and precision medicine. Exosome is a kind of tiny vesicles with a bilayer of phospholipids, which can transfer biological macromolecules to recipients to influence the biological process. M2 macrophages are closely related to the occurrence and development of serious diseases such as tumor. In addition to the traditional concept of macrophage functions such as opsonization, secretion of cytokines and other soluble factors, some studies have found that the exosome derived from M2 macrophages can influence the development of disease by carrying microRNA, long noncodingRNA and functional proteins to regulate target gene expression as well as related proteins synthesis recently. Here, we outlined the biogenesis of the exosome and its biological functions in disease. Then we focused on elucidating the effects of the exosome derived from M2 macrophages on several diseases and its mechanisms. Finally, we discussed the appropriateness and inappropriateness in existing potential applications based on exosomes and macrophages.

Qihui Liu, Yuan Tian, Xiangfeng Zhao, Haifeng Jing, Qi Xie, Peng Li, Dong Li, Dongmei Yan, and Xun Zhu. Mol. Cells 2015;38:886-94. https://doi.org/10.14348/molcells.2015.0125