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. 2017 May 24;12(5):e0174174.
doi: 10.1371/journal.pone.0174174. eCollection 2017.

Is spaceflight-induced immune dysfunction linked to systemic changes in metabolism?

Michael J Pecaut  1 , Xiao Wen Mao  1 , Denise L Bellinger  2 , Karen R Jonscher  3 , Louis S Stodieck  4 , Virginia L Ferguson  4 , Ted A Bateman  5 , Robert P Mohney  6 , Daila S Gridley  1
Affiliations

Is spaceflight-induced immune dysfunction linked to systemic changes in metabolism?

Michael J Pecaut et al. PLoS One. .

Abstract

The Space Shuttle Atlantis launched on its final mission (STS-135) on July 8, 2011. After just under 13 days, the shuttle landed safely at Kennedy Space Center (KSC) for the last time. Female C57BL/6J mice flew as part of the Commercial Biomedical Testing Module-3 (CBTM-3) payload. Ground controls were maintained at the KSC facility. Subsets of these mice were made available to investigators as part of NASA's Bio-specimen Sharing Program (BSP). Our group characterized cell phenotype distributions and phagocytic function in the spleen, catecholamine and corticosterone levels in the adrenal glands, and transcriptomics/metabolomics in the liver. Despite decreases in most splenic leukocyte subsets, there were increases in reactive oxygen species (ROS)-related activity. Although there were increases noted in corticosterone levels in both the adrenals and liver, there were no significant changes in catecholamine levels. Furthermore, functional analysis of gene expression and metabolomic profiles suggest that the functional changes are not due to oxidative or psychological stress. Despite changes in gene expression patterns indicative of increases in phagocytic activity (e.g. endocytosis and formation of peroxisomes), there was no corresponding increase in genes related to ROS metabolism. In contrast, there were increases in expression profiles related to fatty acid oxidation with decreases in glycolysis-related profiles. Given the clear link between immune function and metabolism in many ground-based diseases, we propose a similar link may be involved in spaceflight-induced decrements in immune and metabolic function.

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Conflict of interest statement

Competing Interests: Robert Mohney is an employee of Metabolon, Inc., a fee-for-service metabolomics company, and, as such, has affiliations with or financial involvement with Metabolon, Inc. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Effects of spaceflight on splenocyte phagocytic function.
Flow = Flow cytometry based assay. Plate = 96 well/fluorescence-based assay. Values represent means ± SEM. N = 8 for Ground controls, 5 for Flight. *P<0.001.
Fig 2
Fig 2. Effects of spaceflight on corticosterone and ACTH receptor levels in the adrenal gland.
Corticosterone was quantified via ELISA. Values represent means ± SEM. N = 8 for Ground controls, 5 for Flight. T = trend, P = 0.066. ACTH receptor (ACTH-r) levels quantified via ELISA. p-ACTH-r = phosphorylated ACTH-r. Values represent means ± SEM. N = 11 for Ground controls, 7 for Flight.
Fig 3
Fig 3. Effects of spaceflight on catecholamine levels in the adrenal gland.
Catecholamines measured via HPLC. EPI = epinephrine. NE = Norepinephrine. DA = dopamine. Values represent means ± SEM. N = 13 for Ground controls, 7 for Flight.
Fig 4
Fig 4. Effects of spaceflight on hepatic glycogen stores.
Liver tissue was fixed using 4% paraformaldehyde and stained with Periodic Acid Schiff stain to visualize glycogen. PT = portal triad, CV = central vein. A representative image from n = 5 mice per group is shown.
Fig 5
Fig 5. Effects of spaceflight on GSH production.
This figure represents a combination of data generated through genomics and metabolomics. CTH = cystathionase. cys-gly = cysteinylglycine. GCS = glutamyl-cysteine synthase. GGT = gamma-glutamyl transpeptidase. GS = glutathione synthase. GSH = glutathione. GSSG = glutathione (oxidized). Rectangles represent metabolomics data. Ovals represent genomics data. Grey = unchanged. Green = down-regulated. Red = up-regulated. Blue = specific transaminase unidentified.
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References

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MeSH terms

Grants and funding

This study was supported by NASA managed cooperative agreement NNX10AJ31G and the LLUMC Department of Radiation Medicine. Metabolon provided support in the form of salaries for RM, but did not have any additional role in the study design, decision to publish, or preparation of the manuscript. RM played a role in the study design, data collection, analysis, and preparation of the manuscript.

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