Salivary antimicrobial proteins and stress biomarkers are elevated during a 6-month mission to the International Space Station

Abstract

As the international space community plans for manned missions to Mars, spaceflight-associated immune dysregulation has been identified as a potential risk to the health and safety of the flight crew. There is a need to determine whether salivary antimicrobial proteins, which act as a first line of innate immune defense against multiple pathogens, are altered in response to long-duration (>6 mo) missions. We collected 7 consecutive days of whole and sublingual saliva samples from eight International Space Station (ISS) crewmembers and seven ground-based control subjects at nine mission time points, ~180 and ~60 days before launch (L−180/L−60), on orbit at flight days ~10 and ~90 (FD10/FD90) and ~1 day before return (R−1), and at R+0, R+18, R+33, and R+66 days after returning to Earth. We found that salivary secretory (s)IgA, lysozyme, LL-37, and the cortisol-to-dehydroepiandrosterone ratio were elevated in the ISS crew before (L−180) and during (FD10/FD90) the mission. “Rookie” crewmembers embarking on their first spaceflight mission had lower levels of salivary sIgA but increased levels of α-amylase, lysozyme, and LL-37 during and after the mission compared with the “veteran” crew who had previously flown. Latent herpesvirus reactivation was distinct to the ~6-mo mission crewmembers who performed extravehicular activity (“spacewalks”). Crewmembers who shed at least one latent virus had higher cortisol levels than those who did not shed. We conclude that long-duration spaceflight alters the concentration and/or secretion of several antimicrobial proteins in saliva, some of which are related to crewmember flight experience, biomarkers of stress, and latent viral reactivation. NEW & NOTEWORTHY Spaceflight-associated immune dysregulation may jeopardize future exploration-class missions. Salivary antimicrobial proteins act as a first line of innate immune defense. We report here that several of these proteins are elevated in astronauts during an International Space Station mission, particularly in those embarking on their first space voyage. Astronauts who shed a latent herpesvirus also had higher concentrations of salivary cortisol compared with those who did not shed. Stress-relieving countermeasures are needed to preserve immunity and prevent viral reactivation during prolonged voyages into deep space.

Plasticity of the human IgM repertoire in response to long‐term spaceflight

“…54 Thus, an individual's stress perception and response is a likely contributor to IgM repertoire changes, as previously shown for viral reactivation. 36,52 In line with this, it was shown that exposure to hypergravity of 2 g for 21 days induces an increase in serum corticosterone and a modification of the V(D)J recombination machinery in murine pups. 55 This study is limited by the inherently small sample size, the constraint of manned space missions, and the lack of an age-and sex-matched cosmonaut population remaining on Earth during the mission.…”

“…Such heterogeneity of response to the space exposome has already been noted in flown mice 49 and in astronauts. Indeed, it was observed that 4/8 crewmembers involved in a 6‐month mission on the ISS shed at least one latent type of herpes virus and that this was associated with elevations in salivary cortisol, indicating stress‐induced activation of the hypothalamic‐pituitary adrenal (HPA) axis in these four subjects 52 . Another study showed that 61% of astronauts from ISS missions shed one or more herpes viruses in saliva or urine samples 36 .…”

“…Indeed, it was observed that 4/8 crewmembers involved in a 6-month mission on the ISS shed at least one latent type of herpes virus and that this was associated with elevations in salivary cortisol, indicating stress-induced activation of the hypothalamic-pituitary adrenal (HPA) axis in these four subjects. 52 Another study showed that 61% of astronauts from ISS missions shed one or more herpes viruses in saliva or urine samples. 36 Thus, caveats should be strongly considered before averaging data because this process can hide individual responses.…”

Comment on “Salivary antimicrobial proteins and stress biomarkers are elevated during a 6-month mission to the International Space Station”

“…Despite a number of strengths, there are shortcomings in this paper. This Letter to the Editor addresses the significant effects of light/dark cycles on the salivary changes observed by Agha et al (1). Relevant studies demonstrate that salivary IgA concentrations are controlled by biological rhythms.…”

“…Submitted 23 December 2019; accepted in final form 13 January 2020 TO THE EDITOR: This letter comments on the paper by Agha et al (1) entitled "Salivary antimicrobial proteins and stress biomarkers are elevated during a 6-month mission to the International Space Station" that was published recently in the Journal of Applied Physiology. Agha et al collected saliva samples from International Space Station (ISS) astronauts and groundbased controls.…”