Modulation of Iberian Ribbed Newt Complement Component C3 by Stressors Similar to those Encountered during a Stay Onboard the International Space Station

Guéguinou, Nathan; Jeandel, Jérémy; Kaminski, Sandra; Baatout, Sarah; Ghislin, Stéphanie; Frippiat, Jean-Pol

doi:10.3390/ijms20071579

Cited by 13 publications

(11 citation statements)

References 87 publications

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“…Thus, the modulation of inflammation, which is the immune system’s response to harmful stimuli and is a vital defense mechanism, likely contributes to explaining why nearly half of astronauts spending 6 months onboard the ISS face immunological problems ( 13 ). This modulation of inflammation is multifactorial because both bed rest used to simulate microgravity and the model used to mimic socioenvironmental stresses encountered inflight affect basal levels of cytokines involved in this biological process and is also observed in lower vertebrates in response to stressors similar to those encountered during a stay on the ISS ( 69 ).…”

Section: Discussionmentioning

confidence: 99%

B-Cell Homeostasis Is Maintained During Two Months of Head-Down Tilt Bed Rest With or Without Antioxidant Supplementation

et al. 2022

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Alterations of the immune system could seriously impair the ability to combat infections during future long-duration space missions. However, little is known about the effects of spaceflight on the B-cell compartment. Given the limited access to astronaut samples, we addressed this question using blood samples collected from 20 healthy male volunteers subjected to long-duration bed rest, an Earth-based analog of spaceflight. Hematopoietic progenitors, white blood cells, total lymphocytes and B-cells, four B-cell subsets, immunoglobulin isotypes, six cytokines involved in inflammation, cortisone and cortisol were quantified at five time points. Tibia microarchitecture was also studied. Moreover, we investigated the efficiency of antioxidant supplementation with a cocktail including polyphenols, omega 3, vitamin E and selenium. Our results show that circulating hematopoietic progenitors, white blood cells, total lymphocytes and B-cells, and B-cell subsets were not affected by bed rest. Cytokine quantification suggested a lower systemic inflammatory status, supported by an increase in serum cortisone, during bed rest. These data confirm the in vivo hormonal dysregulation of immunity observed in astronauts and show that bed rest does not alter B-cell homeostasis. This lack of an impact of long-term bed rest on B-cell homeostasis can, at least partially, be explained by limited bone remodeling. None of the evaluated parameters were affected by the administration of the antioxidant supplement. The non-effectiveness of the supplement may be because the diet provided to the non-supplemented and supplemented volunteers already contained sufficient antioxidants. Given the limitations of this model, further studies will be required to determine whether B-cell homeostasis is affected, especially during future deep-space exploration missions that will be of unprecedented durations.

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Section: Discussionmentioning

confidence: 99%

B-Cell Homeostasis Is Maintained During Two Months of Head-Down Tilt Bed Rest With or Without Antioxidant Supplementation

et al. 2022

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“…Modifications noted in these two subjects persisted during the whole mission and up to 30 days after landing, correlated with changes of the V(D)J recombination machinery, coincided with a higher stress response, and likely affected the specificities of the IgM binding sites. These alterations of the antibody repertoire, combined with other immune alterations such as changes in cytokine production, inflammation, and immune cell population distributions and function, 6,8,16,57‐59 could increase the clinical impact on the immune system. Challenge‐type experiments will need to be done to shed light on the consequences of these modifications of the antibody repertoire on immunocompetence and to estimate the effectiveness of inflight vaccination.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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Immune dysregulation is among the main adverse outcomes of spaceflight. Despite the crucial role of the antibody repertoire in host protection, the effects of spaceflight on the human antibody repertoire are unknown. Consequently, using high-throughput sequencing, we examined the IgM repertoire of five cosmonauts 25 days before launch, after 64 ± 11 and 129 ± 20 days spent on the International Space Station (ISS), and at 1, 7, and 30 days after landing. This is the first study of this kind in humans. Our data revealed that the IgM repertoire of the cosmonauts was different from that of control subjects (n = 4) prior to launch and that two out the five analyzed cosmonauts presented significant changes in their IgM repertoire during the mission. These modifications persisted up to 30 days after landing, likely affected the specificities of IgM binding sites, correlated with changes in the V(D)J recombination process responsible for creating antibody genes, and coincided with a higher stress response. These data confirm that the immune system of approximately half of the astronauts who spent 6 months on the ISS is sensitive to spaceflight conditions, and 2 | BUCHHEIM Et al. F I G U R E 4 The cosmonaut IgM repertoire is different from that of the controls. A, Dot blots show individual dispersion indexes for unique VDJ associations in controls (n = 4) and cosmonauts (n = 5) at the beginning of the study (left panel) and 8 months later for controls or 7 days after landing for cosmonauts (right panel). B, Dot blots show the individual frequency of IGHV replacement footprints at the same time points. Statistically significant differences were found using unpaired t tests (A) and Mann-Whitney U tests (B). *P ≤ .

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“…The development of P. waltl larvae under simulated microgravity or simulated microgravity and perturbed circadian rhythm also revealed modifications of the amounts of complement component 3 (C3) mRNAs and/or proteins, suggesting that complement expression can be modified under real spaceflight conditions, potentially increasing the risk of inflammation [ 62 ] and contributing to a better understanding of the inflammation observed during spaceflight [ 63 , 64 , 65 , 66 ]. More recently, Zhu and colleagues [ 67 ] showed that the retinoic acid-inducible gene (RIG)-I-like receptor (RLR) and Toll-like receptor (TLR) signaling pathways, essential for antiviral immunity, are significantly compromised in zebrafish embryos subjected to simulated microgravity.…”

Section: How Can Gepam Contribute To the Understanding Of Moleculamentioning

confidence: 99%

Gravitational Experimental Platform for Animal Models, a New Platform at ESA’s Terrestrial Facilities to Study the Effects of Micro- and Hypergravity on Aquatic and Rodent Animal Models

Bonnefoy

Ghislin

Beyrend

et al. 2021

IJMS

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Using rotors to expose animals to different levels of hypergravity is an efficient means of understanding how altered gravity affects physiological functions, interactions between physiological systems and animal development. Furthermore, rotors can be used to prepare space experiments, e.g., conducting hypergravity experiments to demonstrate the feasibility of a study before its implementation and to complement inflight experiments by comparing the effects of micro- and hypergravity. In this paper, we present a new platform called the Gravitational Experimental Platform for Animal Models (GEPAM), which has been part of European Space Agency (ESA)’s portfolio of ground-based facilities since 2020, to study the effects of altered gravity on aquatic animal models (amphibian embryos/tadpoles) and mice. This platform comprises rotors for hypergravity exposure (three aquatic rotors and one rodent rotor) and models to simulate microgravity (cages for mouse hindlimb unloading and a random positioning machine (RPM)). Four species of amphibians can be used at present. All murine strains can be used and are maintained in a specific pathogen-free area. This platform is surrounded by numerous facilities for sample preparation and analysis using state-of-the-art techniques. Finally, we illustrate how GEPAM can contribute to the understanding of molecular and cellular mechanisms and the identification of countermeasures.

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Modulation of Iberian Ribbed Newt Complement Component C3 by Stressors Similar to those Encountered during a Stay Onboard the International Space Station

Cited by 13 publications

References 87 publications

B-Cell Homeostasis Is Maintained During Two Months of Head-Down Tilt Bed Rest With or Without Antioxidant Supplementation

B-Cell Homeostasis Is Maintained During Two Months of Head-Down Tilt Bed Rest With or Without Antioxidant Supplementation

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

Gravitational Experimental Platform for Animal Models, a New Platform at ESA’s Terrestrial Facilities to Study the Effects of Micro- and Hypergravity on Aquatic and Rodent Animal Models

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