Similar Datasets
Project description:Microgravity is associated with immunological dysfunction, though the underlying mechanisms are poorly understood. Here, using single cell analysis of human peripheral blood mononuclear cells (PBMC)s exposed to short term (25 hours) simulated microgravity, we characterize altered genes and pathways across immune cells under basal and stimulated states with a Toll like Receptor-7/8 agonist. At basal state, simulated microgravity altered the transcriptional landscape across immune cells, with monocyte subsets showing most pathway changes. Remarkably, short term simulated microgravity was sufficient to increase endogenous retroviral and mycobacterial transcripts. Under stimulation in simulated microgravity, nearly all immune cells demonstrated differences in functional pathways. Results from single cell analysis were validated against additional PBMC samples, including by RNA sequencing and super-resolution microscopy, and against data from the Inspiration-4 (i4) mission, JAXA6 mission, Twins study, and spleens from mice housed on the international space station. Combined results show significant impacts of microgravity on pathways essential for optimal immunity, including the cytoskeleton, interferon signaling, pyroptosis, temperature-shock, nuclear receptors, IL-6 signaling, HIF1α, and sirtuin signaling. Using machine learning, we identified numerous compounds linking microgravity to immune cell transcription, and demonstrate that the flavonol, quercetin, can reverse most abnormal pathways. These results offer insight into maladaptation of the immune system in microgravity, and provide opportunities to develop countermeasures that maintain normal immunity in space.
2023-08-01 | GSE218935 | GEO
Project description:Microgravity is associated with immunological dysfunction, though the underlying mechanisms are poorly understood. Here, using single cell analysis of human peripheral blood mononuclear cells (PBMC)s exposed to short term (25 hours) simulated microgravity, we characterize altered genes and pathways across immune cells under basal and stimulated states with a Toll like Receptor-7/8 agonist. At basal state, simulated microgravity altered the transcriptional landscape across immune cells, with monocyte subsets showing most pathway changes. Remarkably, short term simulated microgravity was sufficient to increase endogenous retroviral and mycobacterial transcripts. Under stimulation in simulated microgravity, nearly all immune cells demonstrated differences in functional pathways. Results from single cell analysis were validated against additional PBMC samples, including by RNA sequencing and super-resolution microscopy, and against data from the Inspiration-4 (i4) mission, JAXA6 mission, Twins study, and spleens from mice housed on the international space station. Combined results show significant impacts of microgravity on pathways essential for optimal immunity, including the cytoskeleton, interferon signaling, pyroptosis, temperature-shock, nuclear receptors, IL-6 signaling, HIF1α, and sirtuin signaling. Using machine learning, we identified numerous compounds linking microgravity to immune cell transcription, and demonstrate that the flavonol, quercetin, can reverse most abnormal pathways. These results offer insight into maladaptation of the immune system in microgravity, and provide opportunities to develop countermeasures that maintain normal immunity in space.
2023-08-01 | GSE218936 | GEO
Project description:Microgravity induces a number of significant physiological changes in the cardiovascular, nervous, immune systems, as well as the bone tissue of astronauts. Changes in cell adhesion properties are one aspect affected during long-term spaceflights in mammalian cells. Cellular adhesion behaviors can be divided into cell-cell and cell-matrix adhesion. These behaviors trigger cell-cell recognition, conjugation, migration, cytoskeletal rearrangement, and signal transduction. Cellular adhesion molecule (CAM) is a general term for macromolecules that mediate the contact and binding between cells or between cells and the extracellular matrix (ECM). In this review, we summarize the four major classes of adhesion molecules that regulate cell adhesion, including integrins, immunoglobulin superfamily (Ig-SF), cadherins, and selectin. Moreover, we discuss the effects of spaceflight and simulated microgravity on the adhesion of endothelial cells, immune cells, tumor cells, stem cells, osteoblasts, muscle cells, and other types of cells. Further studies on the effects of microgravity on cell adhesion and the corresponding physiological behaviors may help increase the safety and improve the health of astronauts in space.
| S-EPMC7246714 | biostudies-literature
Project description:Spaceflight and ground-based microgravity analog experiments have suggested that microgravity can affect microbial growth and metabolism. Although the effects of microgravity and its analogs on microorganisms have been studied for more than 50 years, plausible conflicting and diverse results have frequently been reported in different experiments, especially regarding microbial growth and secondary metabolism. Until now, only the responses of a few typical microbes to microgravity have been investigated; systematic studies of the genetic and phenotypic responses of these microorganisms to microgravity in space are still insufficient due to technological and logistical hurdles. The use of different test strains and secondary metabolites in these studies appears to have caused diverse and conflicting results. Moreover, subtle changes in the extracellular microenvironments around microbial cells play a key role in the diverse responses of microbial growth and secondary metabolisms. Therefore, "indirect" effects represent a reasonable pathway to explain the occurrence of these phenomena in microorganisms. This review summarizes current knowledge on the changes in microbial growth and secondary metabolism in response to spaceflight and its analogs and discusses the diverse and conflicting results. In addition, recommendations are given for future studies on the effects of microgravity in space on microbial growth and secondary metabolism.
| S-EPMC5971428 | biostudies-literature
Project description:Exposure to microgravity (µG) during space flights produces a state of immunosuppression, leading to increased viral shedding, which could interfere with long term missions. However, the cellular mechanisms that underlie the immunosuppressive effects of µG are ill-defined. A deep understanding of human immune adaptations to µG is a necessary first step to design data-driven interventions aimed at preserving astronauts' immune defense during short- and long-term spaceflights. We employed a high-dimensional mass cytometry approach to characterize over 250 cell-specific functional responses in 18 innate and adaptive immune cell subsets exposed to 1G or simulated (s)µG using the Rotating Wall Vessel. A statistically stringent elastic net method produced a multivariate model that accurately stratified immune responses observed in 1G and sµG (p value 2E-4, cross-validation). Aspects of our analysis resonated with prior knowledge of human immune adaptations to µG, including the dampening of Natural Killer, CD4+ and CD8+ T cell responses. Remarkably, we found that sµG enhanced STAT5 signaling responses of immunosuppressive Tregs. Our results suggest µG exerts a dual effect on the human immune system, simultaneously dampening cytotoxic responses while enhancing Treg function. Our study provides a single-cell readout of sµG-induced immune dysfunctions and an analytical framework for future studies of human immune adaptations to human long-term spaceflights.
| S-EPMC8184772 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-11-05 | E-GEOD-52057 | biostudies-arrayexpress
Project description:Spaceflight-associated immune system weakening ultimately limits the ability of humans to expand their presence beyond the earth's orbit. A mechanistic study of microgravity-regulated immune cell function is necessary to overcome this challenge. Here, we demonstrate that both spaceflight (real) and simulated microgravity significantly reduce macrophage differentiation, decrease macrophage quantity and functional polarization, and lead to metabolic reprogramming, as demonstrated by changes in gene expression profiles. Moreover, we identified RAS/ERK/NFκB as a major microgravity-regulated pathway. Exogenous ERK and NFκB activators significantly counteracted the effect of microgravity on macrophage differentiation. In addition, microgravity also affects the p53 pathway, which we verified by RT-qPCR and Western blot. Collectively, our data reveal a new mechanism for the effects of microgravity on macrophage development and provide potential molecular targets for the prevention or treatment of macrophage differentiation deficiency in spaceflight.
| S-EPMC8167113 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2013-11-05 | GSE52057 | GEO
Project description:While it has been shown that astronauts suffer immune disorders after spaceflight, the underlying causes are still poorly understood and there are many variables to consider when investigating the immune system in a complex environment. Additionally, there is growing evidence that suggests that not only is the immune system being altered, but the pathogens that infect the host are significantly influenced by spaceflight and ground-based spaceflight conditions. In this study, we demonstrate that Serratia marcescens (strain Db11) was significantly more lethal to Drosophila melanogaster after growth on the International Space Station than ground-based controls, but the increased virulence phenotype of S. marcescens did not persist after the bacterial cultures were passaged on the ground. Increased virulence was also observed in bacteria that were grown in simulated microgravity conditions on the ground using the rotating wall vessel. Increased virulence of the space-flown bacteria was similar in magnitude between wild-type flies and those that were mutants for the well-characterized immune pathways Imd and Toll, suggesting that changes to the host immune system after infection are likely not a major factor contributing towards increased susceptibility of ground-reared flies infected with space-flown bacteria. Characterization of the bacteria shows that at later timepoints spaceflight bacteria grew at a greater rate than ground controls in vitro, and in the host. These results suggest complex physiological changes occurring in pathogenic bacteria in space environments, and there may be novel mechanisms mediating these physiological effects that need to be characterized.
| S-EPMC7000411 | biostudies-literature
Project description:While it has been shown that astronauts suffer immune disorders after spaceflight, the underlying causes are still poorly understood and there are many variables to consider when investigating the immune system in a complex environment. Additionally, there is growing evidence that suggests that not only is the immune system being altered, but the pathogens that infect the host are significantly influenced by spaceflight and ground-based spaceflight conditions. In this study, we demonstrate that Serratia marcescens (strain Db11) was significantly more lethal to Drosophila melanogaster after growth on the International Space Station than ground-based controls, but that the host immune system is not significantly altered amongst known immune genes. High-throughput sequencing of wild-type (w1118) adult hosts infected with either space or ground-reared S. marcescens revealed few changes in gene expression, with 11 genes significantly differentially expressed (q-values <0.05) and only one gene related to the immune system. This data supports the main findings of the paper, which state that both spaceflight and low-shear modeled microgravity conditions increase the virulence of this pathogen, independent of the host immune system. This data, which shows that there are no significant immune-related changes to the host when infected with space-grown sample compared to ground-grown sample, provides further evidence that there are likely phenotypic changes to the pathogen itself that is causing increased virulence in spaceflight and in low-shear modeled microgravity.
2019-09-28 | GSE138116 | GEO