Immunization Induces Inflammation in the Mouse Heart during Spaceflight 2066

Abstract Description Spaceflight-induced immunosuppression has been well documented. However, the consequences of this dysfunction, particularly on other physiological systems, are less known. A sudden exposure to antigen, such as what occurs during vaccination, can elicit myocarditis on Earth, albeit rarely. In spaceflight, microgravity and radiation promote inflammation in organs such as the liver, but not in the heart. We hypothesized that an in-flight exposure to antigen+adjuvant would activate cardiac inflammatory pathways. To this end, we studied tissues collected from 60 8-to-9-week-old female C57BL/6J mice, housed and immunized on the International Space Station for 35 days. Mice received vehicle, primary or secondary exposures to a tetanus toxoid vaccine plus CpG adjuvant. We used RNAseq and RT-qPCR to assess transcriptomic responses. Hearts from mice that received secondary (but not primary) immunization in-flight, had activated NF-κB expression pathways, suggesting an elevated inflammatory response. NF-kB and Stat3 increased by greater than fourfold (p < 0.05). Interestingly, while oxidative stress pathways were not activated, Ingenuity Pathway Analysis predicted macrophage infiltration and cytokine release linked to inflammation and myocarditis. IFNy, a regulator of immunocyte activation and migration, also increased more than twofold (p < 0.05). This study showed that secondary immunization with adjuvant in space has the potential to induce adverse cardiac effects, including myocarditis. Funding Sources The spaceflight portion of this research was funded by NASA grant number NNX13AN34G (to M.J.P). Heart tissue was provided to M.K.-J. as a component of the NASA Biospecimen Sharing Program. Topic Categories Cellular Adhesion, Migration, and Inflammation (CAM)