Immune System Dysregulation During Spaceflight: Potential Countermeasures for Deep Space Exploration Missions

Abstract

Recent studies have established that dysregulation of the human immune system and the reactivation of latent herpesviruses persists for the duration of a 6-month orbital spaceflight. It appears certain aspects of adaptive immunity are dysregulated during flight, yet some aspects of innate immunity are heightened. Interaction between adaptive and innate immunity also seems to be altered. Some crews experience persistent hypersensitivity reactions during flight. This phenomenon may, in synergy with extended duration and galactic radiation exposure, increase specific crew clinical risks during deep space exploration missions. The clinical challenge is based upon both the frequency of these phenomena in multiple crewmembers during low earth orbit missions and the inability to predict which specific individual crewmembers will experience these changes. Thus, a general countermeasure approach that offers the broadest possible coverage is needed. The vehicles, architecture, and mission profiles to enable such voyages are now under development. These include deployment and use of a cis-Lunar station (mid 2020s) with possible Moon surface operations, to be followed by multiple Mars flyby missions, and eventual human Mars surface exploration. Current ISS studies will continue to characterize physiological dysregulation associated with prolonged orbital spaceflight. However, sufficient information exists to begin consideration of both the need for, and nature of, specific immune countermeasures to ensure astronaut health. This article will review relevant in-place operational countermeasures onboard ISS and discuss a myriad of potential immune countermeasures for exploration missions. Discussion points include nutritional supplementation and functional foods, exercise and immunity, pharmacological options, the relationship between bone and immune countermeasures, and vaccination to mitigate herpes (and possibly other) virus risks. As the immune system has sentinel connectivity within every other physiological system, translational effects must be considered for all potential immune countermeasures. Finally, we shall discuss immune countermeasures in the context of their individualized implementation or precision medicine, based on crewmember specific immunological biases.

Exercise as a countermeasure for latent viral reactivation during long duration space flight

“…In summary, this is the first study to report potential protective effects of CRF and upper body muscular endurance on the incidence, severity, and the timing of latent viral reactivation during long duration space travel. While viral reactivation has not hitherto caused widespread clinical problems on the ISS, future exploration class missions (eg, to the lunar or Martian surface) will present much greater challenges to the crew that are expected to further dysregulate immunity and increase the potential for viral reactivation to cause clinical symptoms that require immediate medical attention . As such, countermeasures are necessary to improve or preserve immune function during these extended missions.…”

“…While exercise has long been used to counteract bone and muscle loss due to prolonged periods of weightlessness in space, 11,25 the idea that exercise can protect astronaut immunity has only recently been considered. 1 Indeed, moderate intensity exercise training on Earth has consistently been shown to exert numerous beneficial effects on the immune system, including enhanced immune surveillance, lower frequency of senescent/exhausted T cells, enhanced vaccine response and greater NK-cell cytotoxicity. 12,13,26 The ISS crew in the present study with preflight V O 2max scores classified as "superior" or "excellent" by the ACSM, 23 had a 29% lower risk of reactivating a latent herpesvirus compared to crewmembers with a "good" or "fair" classification.…”

“…37,38 Indeed, a TH 2 -cytokine shift has also been reported in astronauts who reactivated a latent herpes virus during a 14-day shuttle mission, 39 while results from ex vivo studies support that glucocorticoids may enhance EBV reactivation and replication. 37,40 As immune dysregulation during spaceflight is largely seen as a stress-induced phenomenon, 1 we contend that exercise training interventions designed to reduce the effects of stress during space travel (eg, due to confinement, isolation, concerns for own safety, etc) and promote behavioral health may have the added benefit of protecting the immune system. 41 The present findings reporting associations between measures of physical fitness and latent viral reactivation might influence the physical conditioning selection criteria for future exploration class mission crew.…”

“…5 While these have not hitherto caused widespread clinical issues on the ISS, there is concern that additional factors unique to the exploration class environment (eg, elevated radiation exposure, increased isolation, and confinement stress, limited medical provisions with no option for rapid casualty return) could exacerbate an already dysregulated immune system and cause an adverse clinical event in future space explorers. 1 Viral reactivation has the potential to cause a number of clinical symptoms such as mononucleosis, dermatitis, shingles and fever blisters, which could impair crew performance and jeopardize mission success. 1 The reactivation of latent viruses among healthy people on Earth is largely attributed to psychological stress.…”

Building upon current knowledge and techniques of indoor microbiology to construct the next era of theory into microorganisms, health, and the built environment

“…The bacterial community in the gastrointestinal tract of Antarctic visitors decreased in diversity and lost key beneficial members, such as Bifidobacterium [215], both of which can lead to a disrupted intestinal community and risk of disease. Similarly, the sterilization of food and equipment prior to launch, the harsh conditions of space travel, and the isolation from any outside microbial source, contributes to the development of a low-diversity microbial community which is both sparse and tough [28,216,217], and does not make for pleasant company [218][219][220]. The harsh conditions and increase in radiation can contribute to accelerated evolution; a distinct strain of Aspergillus niger was isolated from the International Space Station [221].…”