Microgravity-induced immune dysregulation: phase-specific profiles of differential gene expression

Astronauts experience the reactivation of latent viruses in spaceflight, an indicator of reduced immunity. It is unclear how the immune system responds to pathogens in a microgravity environment. A longitudinal profile of leukocytes' transcriptome changes from participants to an Earth model of microgravity and from astronauts sojourning aboard the International Space Station revealed a reduced expression of immune-related genes while in microgravity. In the current study, we identified transcriptomic changes specific to the transition to and from bed/space, as well as the adaptation, and the recovery from microgravity/space exposure. The expression of immune-related gene shifted in opposite direction at phase transition compared to within the bed rest and reambulation phases. Differential expression of cytokine genes supported a reduced immune-response during the head down tilt bed rest phase and return to baseline levels at reambulation. Immunoglobulin gene expression increased after participants left the facility. The enrichment analysis of the differentially expressed genes identified the gene ontology terms virus/viral and genes previously involved in the modulation of the response to latent reactivation, including IFNL1, TNFSF14, IL10, and ISG15. Leukocytes' transcriptomic analysis revealed dynamic changes of immune-related gene expression timed with phases of spaceflight. The current analysis combined with previous evidence of herpesvirus reactivation during space mission represent a valuable model for the study of viral latency in vivo.