Monocytes reprogrammed by tumor microparticle vaccine inhibit tumorigenesis and tumor development.

Tumor microparticles (T-MPs) are considered as a tumor vaccine candidate. Although some studies have analyzed the mechanism of T-MPs as tumor vaccine, we still lack understanding of how T-MPs stimulate a strong anti-tumor immune response. Here, we show that T-MPs induce macrophages to release a key chemotactic factor CCL2, which attracts monocytes to the vaccine injection site and enhances endocytosis of antigen. Monocytes subsequently enter the draining lymph node, and differentiate into monocyte-derived DCs (moDCs), which present tumor antigens to T lymphocytes and deliver a potent anti-tumor immune response. Mechanically, T-MPs activate the cGAS-STING signaling through DNA fragments, and then induce monocytes to upregulate the expression of IRF4, which is a key factor for monocyte differentiation into moDCs. More importantly, monocytes that have endocytosed T-MPs acquire the ability to treat tumors. Collectively, this work might provide novel vaccination strategy for the development of tumor vaccines and facilitate the application of T-MPs for clinic oncotherapy. Supplementary Information: The online version contains supplementary material available at 10.1186/s12645-023-00190-x.

Contribution of prgH gene for Salmonella Pullorum to virulence and the expression of NLRP3, Caspase-1 and IL-1ß in chickens.

Type III secretion system 1 (T3SS1) encoded by Salmonella pathogenicity island 1 (SPI1) is associated with invasion of host cells by Salmonella, PrgH encoded by prgH gene is an important component of T3SS1. This study aimed to explore the contribution of prgH gene for Salmonella Pullorum to virulence and the expression of NLRP3, Caspase-1 and IL-1ß in chickens. A prgH gene deletion mutant (C79-13ΔprgH) was firstly generated, and the result of LD50 showed that deletion of prgH significantly decreased the virulence of Salmonella Pullorum in one-day-old HY-line white chickens, and the colonization also decreased in chickens after loss of prgH. Next, the expressions of NLRP3, Caspase-1, and IL-1ß were detected in acute infection model of chickens by qRT-PCR and/or ELISA, respectively, and the results showed that the mutant strain C79-13ΔprgH reduced the expression levels of NLRP3, Caspase-1, and IL-1ß in chickens compared to the group infected with the wild type strain C79-13. Taken together, all of these findings indicated that prgH promotes the virulence and the expression of NLRP3, Caspase-1, and IL-1ß for Salmonella Pullorum in chickens.

Salmonella Pullorum lacking srfA is attenuated, immunogenic and protective in chickens.

Sallmonella Pullorum is a host-restricted pathogen for poultry and causes severe economic importance in many developing countries. The development of novel vaccines for Salmonella Pullorum is necessary to eradicate the prevalence of the pathogen. In our study, a srfA deletion mutant (C79-13ΔsrfA) of Salmonella Pullorum was constructed, and then the biological characteristics and protective efficacy of the mutant were evaluated. The mutant C79-13ΔsrfA was much less virulent than its parental strain C79-13 in one-day-old HY-line white chickens, immunization with C79-13ΔsrfA (4 × 107 CFU) through oral pathway induced highly specific humoral and cellular immune responses, the growth performance of vaccinated chickens was consistent with that of unvaccinated chickens. The survival percentages of vaccinated chickens reached 90% and 80%, after challenge with Salmonella Pullorum strain C79-13 and Salmonella Gallinarum strain SG9 at 10 days post-immunization (dpi), respectively. Collectively, our results indicate that C79-13ΔsrfA is a live attenuated vaccine candidate.

Predator-driven intra-species variation in locomotion, metabolism and water velocity preference in pale chub (Zacco platypus) along a river.

Fish inhabit environments that vary greatly in terms of predation intensity, and these predation regimes are generally expected to be a major driver of divergent natural selection. To test whether there is predator-driven intra-species variation in the locomotion, metabolism and water velocity preference of pale chub (Zacco platypus) along a river, we measured unsteady and steady swimming and water velocity preference among fish collected from both high- and low-predation habitats in the Wujiang River. We also measured the routine metabolic rate (RMR), maximum metabolic rate (MMR) and cost of transport (COT) and calculated the optimal swimming speed (Uopt). The fish from the high-predation populations showed a shorter response latency, elevated routine metabolism, lower swimming efficiency at low swimming speed and lower water velocity preference compared with those from the low-predation populations. Neither of the kinematic parameters fast-start and critical swimming speed (Ucrit) showed a significant difference between the high- and low-predation populations. The fish from the high-predation populations may improve their predator avoidance capacity primarily through an elevated routine metabolism and shorter response latency to achieve advanced warning and escape, rather than an improved fast-start swimming speed or acceleration. Thus, the cost of this strategy is an elevated RMR, and no trade-off between unsteady and steady swimming performance was observed in the pale chub population under various predation stresses. It was interesting to find that the high-predation fish showed an unexpected lower velocity preference, which might represent a compromise between predation avoidance, foraging and energy saving.