Post-Spaceflight (STS-135) Mouse Splenocytes Demonstrate Altered Activation Properties and Surface Molecule Expression

Abstract

Alterations in immune function have been documented during or post-spaceflight and in ground based models of microgravity. Identification of immune parameters that are dysregulated during spaceflight is an important step in mitigating crew health risks during deep space missions. The in vitro analysis of leukocyte activity post-spaceflight in both human and animal species is primarily focused on lymphocytic function. This report completes a broader spectrum analysis of mouse lymphocyte and monocyte changes post 13 days orbital flight (mission STS-135). Analysis includes an examination in surface markers for cell activation, and antigen presentation and co-stimulatory molecules. Cytokine production was measured after stimulation with T-cell mitogen or TLR-2, TLR-4, or TLR-5 agonists. Splenocyte surface marker analysis immediate post-spaceflight and after in vitro culture demonstrated unique changes in phenotypic populations between the flight mice and matched treatment ground controls. Post-spaceflight splenocytes (flight splenocytes) had lower expression intensity of CD4+CD25+ and CD8+CD25+ cells, lower percentage of CD11c+MHC II+ cells, and higher percentage of CD11c+MHC I+ populations compared to ground controls. The flight splenocytes demonstrated an increase in phagocytic activity. Stimulation with ConA led to decrease in CD4+ population but increased CD4+CD25+ cells compared to ground controls. Culturing with TLR agonists led to a decrease in CD11c+ population in splenocytes isolated from flight mice compared to ground controls. Consequently, flight splenocytes with or without TLR-agonist stimulation showed a decrease in CD11c+MHC I+, CD11c+MHC II+, and CD11c+CD86+ cells compared to ground controls. Production of IFN-γ was decreased and IL-2 was increased from ConA stimulated flight splenocytes. This study demonstrated that expression of surface molecules can be affected by conditions of spaceflight and impaired responsiveness persists under culture conditions in vitro.

Gene-metabolite profile integration to understand the cause of spaceflight induced immunodeficiency

“…Our omics results supported previous reports about the influence of microgravity on the immunological machinery. 13 , 28 – 30 A decreased functionality of immune health and altered corticosterone and lymphocyte abundance in microgravity were observed in both human and rodent cohorts flown into space. 31 – 34 Blood samples collected from astronauts showed an overall immunosuppression in response to LPS stimulation in vitro.…”

Spaceflight and simulated microgravity suppresses macrophage development via altered RAS/ERK/NFκB and metabolic pathways

“…Recently, the effects of microgravity on immune function have received increased attention and have been investigated using astronaut leukocytes, 5 space-flown mice and rats, 6,7 and in vitro cell culture. 8 Together, data from the International Space Station, Skylab, and space shuttle suggest that dysregulated immune cell-mediated cytokine secretion is a major mechanism leading to spaceflightassociated immune dysfunction.…”

Characterization of Aspergillus fumigatus Isolates from Air and Surfaces of the International Space Station

“…Our understanding of how the stressors of such environments, which include microgravity and increased exposure to irradiation, influence microbial biology over time remains in its infancy (2). Changes in microbial community composition and microbial species characteristics have the potential to affect human health and safety, particularly in light of the fact that extended periods of time in space have been shown to alter vertebrate and human immunity (3, 4). Furthermore, as durations of manned space missions increase, such as going to Mars, it becomes of heightened importance to understand the breadth and potential consequences of host-microbe interactions in crew habitation.…”

“…Furthermore, as durations of manned space missions increase, such as going to Mars, it becomes of heightened importance to understand the breadth and potential consequences of host-microbe interactions in crew habitation. There exists an unmet need for studies characterizing individual microbial species isolated directly from space environments, as sampling experiments to date have aimed at understanding changes in microbial community composition at the species level (4–6), and it has been documented that simulated space environments provide a poor comparison for what is actually observed in orbit (7), highlighting a need for additional experimentation with samples derived from space environments.…”