Simulated Microgravity affects immune reaction to infection through altering lymphocyte differentiation, cytokine...

Microgravity is one of the most significant hazards during spaceflight, as prolonged exposure to the microgravity environment impairs the immune system and increases the risk of infection. Extensive research on the effects of microgravity on the immune system was conducted. However, the immune reaction to infection under microgravity remains unclear. In this study, we established a hindlimb unloading mouse model to simulate the effects of microgravity, and then lipopolysaccharide (LPS) stimulation was administered to simulate infection. Transcriptomic profiling (RNA-seq) of blood cells revealed that simulated microgravity affected the immune response to infection. Before LPS stimulation, simulated microgravity significantly increased the levels of IL-1β, IL-6, and platelet count. Following LPS administration, time-course analysis showed that simulated microgravity altered the temporal dynamics of both lymphocyte subsets and cytokines. Peritoneal macrophage polarization analysis demonstrated that simulated microgravity inhibited M2 polarization both before and during the early stage of LPS stimulation. These findings indicate that simulated microgravity compromises immune function and dysregulates the immune response to infection through affecting lymphocyte differentiation, cytokine secretion, and macrophage polarization.