Abstract
Extended space missions are known to induce stress and immune dysregulation. Hindlimb unloading is a ground-based model used to reproduce most spaceflight conditions. The aim of this study was to better characterize the consequences of prolonged exposure to hindlimb unloading on murine splenic lymphocyte sub-populations. To ensure that the observed changes were not due to tail restraint but to the antiorthostatic position, three groups of mice were used: control (C), orthostatic restrained (R) and hindlimb unloaded (HU). After 21 days of exposure, no difference in serum corticosterone levels nor in thymus and spleen weights were observed between HU mice and their counterparts, revealing a low state of stress. Interestingly, flow cytometric analyses showed that B cells were drastically reduced in HU mouse spleens by 59% and, while the T cells number did not change, the Th/Tc ratio was decreased. Finally, the use of a fluorescent dye monitoring lymphoproliferation demonstrated that lymphocyte response to mitogen was reduced in Th and Tc populations and to a greater extent in B cells. Thus, we showed for the first time that, even if restraint has its own effects on the animals and their splenic lymphocytes, the prolonged antiorthostatic position leads, despite the absence of stress, to an inversion of the B/T ratio in the spleen. Furthermore, the lymphoproliferative response was impaired with a strong impact on B cells. Altogether, these results suggest that B cells are more affected by hindlimb unloading than T cells which may explain the high susceptibility to pathogens, such as gram-negative bacteria, described in animal models and astronauts.
Highlights
Human presence is currently expanding into low Earth orbit and beyond, with the ability to visit space for longer periods of time in the International Space Station and planned missions to Mars
The C mice grew regularly while both R and hindlimb unloaded (HU) mice exhibited a significant drop in body weight during the first three days, but no further decrease was observed over the days (Fig. 1)
R mice recovered their initial weight on day 8, whereas HU mice returned to their initial weight on day 15
Summary
Human presence is currently expanding into low Earth orbit and beyond, with the ability to visit space for longer periods of time in the International Space Station and planned missions to Mars. There have been a large number of studies to understand how this extreme environment affects various physiological functions, especially the immune system [1,2]. Crucian et al [11] have recently indicated that this immune dysregulation may depend on mission characteristics such as duration. This was especially true for antibody production, which was not changed during short-term spaceflight [12], while long-term missions showed more severe effects [13,14]. Our previous studies have demonstrated that long-term missions affect immunoglobulin gene expression [15,16,17] and antibody somatic hypermutation frequency [18,19]. Before undertaking prolonged space missions, it is important to determine which mechanisms are involved in the spaceflight-induced changes in humoral immunity, which up to now have rarely been investigated
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