Spaceflight impairs antigen‐specific tolerance induction in vivo and increases inflammatory cytokines

Abstract

The health risks of a dysregulated immune response during spaceflight are important to understand as plans emerge for humans to embark on long-term space travel to Mars. In this first-of-its-kind study, we used adoptive transfer of T-cell receptor transgenic OT-II CD4 T cells to track an in vivo antigen-specific immune response that was induced during the course of spaceflight. Experimental mice destined for spaceflight and mice that remained on the ground received transferred OT-II cells and cognate peptide stimulation with ovalbumin (OVA) 323-339 plus the inflammatory adjuvant, monophosphoryl lipid A. Control mice in both flight and ground cohorts received monophosphoryl lipid A alone without additional OVA stimulation. Numbers of OT-II cells in flight mice treated with OVA were significantly increased by 2-fold compared with ground mice treated with OVA, suggesting that tolerance induction was impaired by spaceflight. Production of proinflammatory cytokines were significantly increased in flight compared with ground mice, including a 5-fold increase in IFN-g and a 10-fold increase in IL-17. This study is the first to show that immune tolerance may be impaired in spaceflight, leading to excessive inflammatory responses.-Chang, T. T., Spurlock, S. M, Candelario, T. L. T., Grenon, S. M., Hughes-Fulford, M. Spaceflight impairs antigen-specific tolerance induction in vivo and increases inflammatory cytokines. FASEB J. 29, 4122-4132 (2015). www.fasebj.org

Prolonged exposure to simulated microgravity diminishes dendritic cell immunogenicity

“…However, as our data demonstrates, long-term exposure of DC to SMG results in a reduction of CD4 + T cell IL-2 production. The loss of IL-2 production has been demonstrated during the course of several space flights using both assessment of astronaut serum levels and the activation of peripheral blood mononuclear cells (PBMC) by agent-mediated direct stimulation of activation pathways 38 . Together with our findings in this report and previously those concerning T cell activity in SMG, short-term exposure to SMG accentuates the functions of both DC and T cells, producing elevated IL-2 compared to Static cultures.…”

Reproducible changes in the gut microbiome suggest a shift in microbial and host metabolism during spaceflight

“…This lack of similarity implies that the gut microbiome is modulated largely by space environmental factors other than radiation during spaceflight. Given the differences in experimental conditions between Flight and Ground groups discussed above, we hypothesize that spaceflight-associated microbiome changes can be largely attributed to microgravity, which may influence microbial physiology and growth via low fluid shear dynamics [19, 20] and host physiological responses including altered digesta propulsion and digestive function [21], inflammation [22], fluid shift, and cardiovascular functions [23]. Microgravity also enables the animals to explore the three-dimensional space more easily in the rodent habitat, thus allowing behavioral changes that may be related to coping with stressors such as confinement.…”

From the bench to exploration medicine: NASA life sciences translational research for human exploration and habitation missions

“… 23 NASA has a successful record in this domain that should continue, for example, with its BioSpecimen Sharing Programs. Researchers have recently shared tissues from specific animals on a late Shuttle mission (STS-131), 24 – 31 and the most recent Russian Bion biosatellite mission; 32 – 35 sharing was in the form of preserved tissues from NASA’s Life Sciences Data Archive. 36 Further, new Omic-science studies like NASA’s emerging GeneLab open-science data and biosample repository 37 and the recent astronaut Twins Study 38 enable big-data collection, analytics, and horizontal integration.…”