The Emerging Role of Macrophages in Immune System Dysfunction under Real and Simulated Microgravity Conditions

Abstract

In the process of exploring space, the astronaut’s body undergoes a series of physiological changes. At the level of cellular behavior, microgravity causes significant alterations, including bone loss, muscle atrophy, and cardiovascular deconditioning. At the level of gene expression, microgravity changes the expression of cytokines in many physiological processes, such as cell immunity, proliferation, and differentiation. At the level of signaling pathways, the mitogen-activated protein kinase (MAPK) signaling pathway participates in microgravity-induced immune malfunction. However, the mechanisms of these changes have not been fully elucidated. Recent studies suggest that the malfunction of macrophages is an important breakthrough for immune disorders in microgravity. As the first line of immune defense, macrophages play an essential role in maintaining homeostasis. They activate specific immune responses and participate in large numbers of physiological activities by presenting antigen and secreting cytokines. The purpose of this review is to summarize recent advances on the dysfunction of macrophages arisen from microgravity and to discuss the mechanisms of these abnormal responses. Hopefully, our work will contribute not only to the future exploration on the immune system in space, but also to the development of preventive and therapeutic drugs against the physiological consequences of spaceflight.

The Effects of Simulated Microgravity on Macrophage Phenotype

“…Our results show that pro-inflammatory TNF-α secretion by macrophage cells in simulated microgravity was significantly decreased across all three phenotypes evaluated. This agrees with current literature on the downregulation of TNF-α protein expression by macrophages in microgravity [ 11 ]. A review of literature highlights the differences in results seen across studies, with some studies reporting increases in TNF-α expression [ 55 , 56 , 57 ] and others reporting decreases [ 5 , 19 , 20 , 21 ] from µG, suggesting that the variety of cell types, microgravity system, duration, and methods used could be contributing factors [ 10 ].…”

“…Published data on the effect of altered gravity on macrophages have not extensively considered the role of macrophage phenotypes. Macrophage microgravity studies in general have shown variable results and are relatively limited [ 10 , 11 ]. Overall, macrophages demonstrate many sensitivities to changes in gravity, both in their short- and long-term responses.…”

“…Other opportunities to expose cells to real microgravity include suborbital flight/sounding rocket and parabolic flight modalities, however, these face many of the same challenges. Alternatives to real microgravity include a variety of methods commonly used to expose cultured cells to simulated microgravity, including several benchtop methods, such as clinorotation and random position machines [ 10 , 11 ]. In this work, we utilize a rotary cell culture system (RCCS), specifically the rotating wall vessel (RWV) originally developed by the National Aeronautics and Space Administration, to expose phenotypically divergent macrophages to simulated microgravity and assess the acute biological effects.…”

Microgravity and Space Medicine

“…In addition, Sun et al [23] reviewed the current knowledge about the dysfunction of macrophages exposed to µg and discussed the mechanisms of these abnormal responses.…”

“…[20] Influence of gravitational changes on proliferative processes and calcium homeostasis. [13] In addition, the SI covers five reviews (Table 2) [10,[22][23][24][25]. These 16 excellent papers were published as detailed in Tables 1 and 2.…”