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NASA NTRS2011

Immune System Dysregulation and Latent Herpesvirus Reactivation During Winterover at Concordia Station, Dome C, Antarctica

Immune system dysregulation occurs during spaceflight and consists of altered peripheral leukocyte distribution, reductions in immunocyte function and altered cytokine production profiles. Causes may include stress, confinement, isolation, and disrupted circadian rhythms. All of these factors may be replicated to some degree in terrestrial environments. NASA is currently evaluating the potential for a ground-based analog for immune dysregulation, which would have utility for mechanistic investigations and countermeasures evaluation. For ground-based space physiology research, the choice of terrestrial analog must carefully match the system of interest. Antarctica winter-over, consisting of prolonged durations in an extreme/dangerous environment, station-based habitation, isolation and disrupted circadian rhythms, is potentially a good ground-analog for spaceflight-associated immune dysregulation. Of all Antarctica bases, the French-Italian Concordia Station, may be the most appropriate to replicate spaceflight/exploration conditions. Concordia is an interior base located in harsh environmental conditions, and has been constructed to house small, international crews in a station-environment similar to what should be experienced by deep space astronauts. The ESA-NASA CHOICE study assessed innate and adaptive immunity, viral reactivation and stress factors during Concordia winterover deployment. The study was conducted over two winterover missions in 2009 and 2010. Final study data from NASA participation in these missions will be presented.

Crucian, B. E.↗

NASA NTRS2012

Plasma Cytokine Levels During Long-Duration Spaceflight

Determine the in-flight status of immunity, physiological stress, viral immunity/reactivation. Specific measurements include leukocyte distribution, T cell function, cytokine production profiles (mRNA, intracellular, secreted, plasma), virus-specific T cell number/function, latent herpesvirus reactivation, stress hormone levels. Determine the clinical risk related to immune dysregulation for exploration class spaceflight, as well as an appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures. Specific Study Objectives: Determine the nutritional status of astronauts before, during, and after spaceflight ensure adequate intake of energy, protein, and vitamins during missions. The Clinical Nutritional Status Assessment measures dietary intake, body composition, protein, bone, iron, mineral, vitamin, and antioxidant status (60 total analytes). Currently, it is a medical requirement for U.S. crewmembers on-board the ISS. The results of data analysis are used both to understand the connections between nutrition and human health during space flight, and to develop effective dietary strategies to reduce adverse health impacts (including bone loss, loss of important vitamins and minerals, and increased genetic damage from radiation).

Crucian, Brian E.↗

NASA NTRS2013

Plasma Cytokine Concentrations Indicate In-vivo Hormonal Regulation of Immunity is Altered During Long-Duration Spaceflight

Background: Aspects of immune system dysregulation associated with long‐duration spaceflight have yet to be fully characterized, and may represent a clinical risk to crewmembers during deep space missions. Plasma cytokine concentration may serve as an indicator of in vivo physiological changes or immune system mobilization. Methods: The plasma concentrations of 22 cytokines were monitored in 28 astronauts during long‐duration spaceflight onboard the International Space Station. Blood samples were collected three times before flight, 3‐5 times during flight (depending on mission duration), at landing and 30 days post‐landing. Analysis was performed by bead array immunoassay. Results: With few exceptions, minimal detectable mean plasma levels (<10 pg/ml) were observed at baseline (launch minus 180) for innate inflammatory cytokines or adaptive regulatory cytokines, however IL‐1ra and several chemokines were constitutively present. An increase in the plasma concentration IL‐8, IL‐1ra, Tpo, CCL4, CXCL5, TNF(alpha), GM‐CSF and VEGF was observed associated with spaceflight. Significant post‐flight increases were observed for IL‐6 and CCL2. No significant alterations were observed during or following spaceflight for adaptive/T‐regulatory cytokines (IL‐2, IFN(gamma), IL‐17, IL4, IL‐5, IL‐10). Conclusions: This pattern of cytokine dysregulation suggests multiple physiological adaptations persist during flight, including inflammation, leukocyte recruitment, angiogenesis and thrombocyte regulation.

Crician, Brian E.↗

NASA NTRS2013

Terrestrial Spaceflight Analogs: Antarctica

Alterations in immune cell distribution and function, circadian misalignment, stress and latent viral reactivation appear to persist during Antarctic winterover at Concordia Station. Some of these changes are similar to those observed in Astronauts, either during or immediately following spaceflight. Others are unique to the Concordia analog. Based on some initial immune data and environmental conditions, Concordia winterover may be an appropriate analog for some flight-associated immune system changes and mission stress effects. An ongoing smaller control study at Neumayer III will address the influence of the hypoxic variable. Changes were observed in the peripheral blood leukocyte distribution consistent with immune mobilization, and similar to those observed during spaceflight. Alterations in cytokine production profiles were observed during winterover that are distinct from those observed during spaceflight, but potentially consistent with those observed during persistent hypobaric hypoxia. The reactivation of latent herpesviruses was observed during overwinter/isolation, that is consistently associated with dysregulation in immune function.

Crucian, Brian↗

NASA NTRS2014

HEMODOSE: A Set of Multi-parameter Biodosimetry Tools

After the events of September 11, 2001 and recent events at the Fukushima reactors in Japan, there is an increasing concern of the occurrence of nuclear and radiological terrorism or accidents that may result in large casualty in densely populated areas. To guide medical personnel in their clinical decisions for effective medical management and treatment of the exposed individuals, biological markers are usually applied to examine the radiation induced changes at different biological levels. Among these the peripheral blood cell counts are widely used to assess the extent of radiation induced injury. This is due to the fact that hematopoietic system is the most vulnerable part of the human body to radiation damage. Particularly, the lymphocyte, granulocyte, and platelet cells are the most radiosensitive of the blood elements, and monitoring their changes after exposure is regarded as the most practical and best laboratory test to estimate radiation dose. The HEMODOSE web tools are built upon solid physiological and pathophysiological understanding of mammalian hematopoietic systems, and rigorous coarse-grained biomathematical modeling and validation. Using single or serial granulocyte, lymphocyte, leukocyte, or platelet counts after exposure, these tools can estimate absorbed doses of adult victims very rapidly and accurately. Some patient data in historical accidents are utilized as examples to demonstrate the capabilities of these tools as a rapid point-of-care diagnostic or centralized high-throughput assay system in a large scale radiological disaster scenario. Unlike previous dose prediction algorithms, the HEMODOSE web tools establish robust correlations between the absorbed doses and victim's various types of blood cell counts not only in the early time window (1 or 2 days), but also in very late phase (up to 4 weeks) after exposure

Hu, Shaowen↗

NASA NTRS2014

HEMODOSE: A Set of Multi-parameter Biodosimetry Tools

There continues to be important concerns of the possibility of the occurrence of acute radiation syndromes following nuclear and radiological terrorism or accidents that may result in mass casualties in densely populated areas. To guide medical personnel in their clinical decisions for effective medical management and treatment of the exposed individuals, biological markers are usually applied to examine radiation induced biological changes to assess the severity of radiation injury to sensitive organ systems. Among these the peripheral blood cell counts are widely used to assess the extent of radiation induced bone marrow (BM) injury. This is due to the fact that hematopoietic system is a vulnerable part of the human body to radiation damage. Particularly, the lymphocyte, granulocyte, and platelet cells are the most radiosensitive of the blood elements, and monitoring their changes after exposure is regarded as a practical and recommended laboratory test to estimate radiation dose and injury. In this work we describe the HEMODOSE web tools, which are built upon solid physiological and pathophysiological understanding of mammalian hematopoietic systems, and rigorous coarse-grained biomathematical modeling and validation. Using single or serial granulocyte, lymphocyte, leukocyte, or platelet counts after exposure, these tools can estimate absorbed doses of adult victims very rapidly and accurately to assess the severity of BM radiation injury. Some patient data from historical accidents are utilized as examples to demonstrate the capabilities of these tools as a rapid point-of-care diagnostic or centralized high-throughput assay system in a large-scale radiological disaster scenario. HEMODOSE web tools establish robust correlations between the absorbed doses and victim's various types of blood cell counts not only in the early time window (1 or 2 days), but also in very late phase (up to 4 weeks) after exposure.

Hu, Shaowen↗

NASA NTRS2014

Pulmonary and Systemic Immune Response to Chronic Lunar Dust Inhalation

Background: Due to millennia of meteorite impact with virtually no erosive effects, the surface of the Moon is covered by a layer of ultra‐fine, reactive Lunar dust. Very little is known regarding the toxicity of Lunar dust on human physiology. Given the size and electrostatic characteristics of Lunar dust, countermeasures to ensure non‐exposure of astronauts will be difficult. To ensure astronaut safety during any future prolonged Lunar missions, it is necessary to establish the effect of chronic pulmonary Lunar dust exposure on all physiological systems. Methods: This study assessed the toxicity of airborne lunar dust exposure in rats on pulmonary and system immune system parameters. Rats were exposed to 0, 20.8, or 60.8 mg/m3 of lunar dust (6h/d; 5d/wk) for up to 13 weeks. Sacrifices occurred after exposure durations of 1day, 7 days, 4 weeks and 13 weeks post‐exposure, when both blood and lung lavage fluid were collected for analysis. Lavage and blood assays included leukocyte distribution by flow cytometry, electron/fluorescent microscopy, and cytokine concentration. Cytokine production profiles following mitogenic stimulation were performed on whole blood only. Results: Untreated lavage fluid was comprised primarily of pulmonary macrophages. Lunar dust inhalation resulted in an influx of neutrophils and lymphocytes. Although the percentage of lymphocytes increased, the T cell CD4:CD8 ratio was unchanged. Cytokine analysis of the lavage fluid showed increased levels of IL‐1b and TNFa. These alterations generally persisted through the 13 week sampling. Blood analysis showed few systemic effects from the lunar dust inhalation. By week 4, the peripheral granulocyte percentage was elevated in the treated rats. Plasma cytokine levels were unchanged in all treated rats compared to controls. Peripheral blood analysis showed an increased granulocyte percentage and altered cytokine production profiles consisting of increased in IL‐1b and IL‐6, and decreased IL‐2 production. Conclusion: Lunar dust inhalation results in significant lung inflammation, and some systemic effects, that does not resolve through 13 weeks. Lunar dust may therefore represent a crew health risk during sortie or long‐duration Lunar missions.

Crucian, Brian↗

NASA NTRS2014

A Multiple Parameters Biodosimetry Tool with Various Blood Cell Counts - the Hemodose Approach

There continue to be important concerns about the possibility of the occurrence of acute radiation syndromes following nuclear and radiological terrorism or accidents that may result in mass casualties in densely populated areas. To guide medical personnel in their clinical decisions for effective medical management and treatment of the exposed individuals, biological markers are usually applied to examine radiation induced biological changes to assess the severity of radiation injury to sensitive organ systems. Among these the peripheral blood cell counts are widely used to assess the extent of radiation induced bone marrow injury. This is due to the fact that the hematopoietic system is the most vulnerable part of the human body to radiation damage. Particularly, the lymphocyte, granulocyte, and platelet cells are the most radiosensitive of the blood elements, and monitoring their changes after exposure is regarded as a practical and recommended laboratory test to estimate radiation dose and injury. Based upon years of physiological and pathophysiological investigation of mammalian hematopoietic systems, and rigorous coarse-grained bio-mathematical modeling and validation on species from mouse, to dog, monkey, and human, we have developed a set of software tools Hemodose, which can use single or serial granulocyte, lymphocyte, leukocyte, or platelet counts after exposure to estimate absorbed doses of adult victims very rapidly and accurately. Some patient data from historical accidents are utilized as examples to demonstrate the capabilities of these tools as a rapid point-of-care diagnostic or centralized high-throughput assay system in a large-scale radiological disaster scenario. Most significant to the improvement of national and local preparedness of a potential nuclear/radiological disaster, this HemoDose approach establishes robust correlations between the absorbed doses and victim's various types of blood cell counts not only in the early time window (1 or 2 days), but also in the very late phase (up to 4 weeks) after exposure.

Hu, Shaowen↗

NASA NTRS2015

Risk of Crew Adverse Health Event Due to Altered Immune Response

Determining the effect of space travel on the human immune system has proven to be extremely challenging. Limited opportunities for in-flight studies, varying mission durations, technical and logistical obstacles, small subject numbers, and a broad range of potential assays have contributed to this problem. Additionally, the inherent complexity of the immune system, with its vast array of cell populations, sub-populations, diverse regulatory molecules, and broad interactions with other physiological systems, makes determining precise variables to measure very difficult. There is also the challenge of determining the clinical significance of any observed immune alterations. Will such a change lead to disease, or is it a transient subclinical observation related to short-term stress? The effect of this problem may be observed by scanning publications associated with immunity and spaceflight, which began to appear during the 1970s. Although individually they are each valid studies, the comprehensive literature to date suffers from widely varying sampling methods and assay techniques, low subject counts, and sometimes a disparate focus on narrow aspects of immunity. The most clinically relevant data are derived from in-flight human studies, which have demonstrated altered cell-mediated immunity and reactivation of latent herpes viruses. Much more data are available from post-flight testing of humans, with clear evidence of altered cytokine production patterns, altered leukocyte distribution, continued latent viral reactivation, and evidence of dramatically altered virus-specific immunity. It is unknown if post-flight assessments relate to the in-flight condition or are a response to landing stress and readaptation. In-flight culture of cells has clearly demonstrated that immune cells are gravity-sensitive and display altered functional characteristics. It is unknown if these data are related to in vivo immune cell function or are an artifact of microgravity culture. Ground analog testing of humans and animals, as well as microgravity-analog cell culture, has demonstrated utility. However, in all cases, it is not known with certainty if these data would reflect similar testing during space travel. Given their ready availability, ground analogs may be extremely useful for assay development and the evaluation of potential countermeasures. In general, the evidence base suffers from widely disparate studies on small numbers of subjects that do not directly correlate well with each other or spaceflight itself. Also lacking are investigations of the effect of gender on adaption to spaceflight. This results in significant knowledge 'gaps' that must be filled by future studies to completely determine any clinical risk related to immunity for human exploration-class space missions. These gaps include a significant lack of in-flight data, particularly during long-duration space missions. The International Space Station represents an excellent science platform with which to address this knowledge gap. Other knowledge gaps include lack of a single validated ground analog for the phenomenon and a lack of flight-compatible laboratory equipment capable of monitoring astronauts (for either clinical or research purposes). However, enough significant data exist, as described in this manuscript, to warrant addressing this phenomenon during the utilization phase of the ISS. A recent Space Shuttle investigation has confirmed the 31 in-flight nature of immune dysregulation, demonstrating that it is not merely a post-flight phenomenon. Several current studies are ongoing onboard the ISS that should thoroughly characterize the phenomenon. NASA recognizes that if spaceflight-associated immune dysregulation persists during exploration flights in conjunction with other dangers, such as high-energy radiation, the result may be a significant clinical risk. This emphasizes the need for a continued integrated comprehensive approach to determining the effect of prolonged spaceflight, separated from transient launch and landing stresses, on human immunity. After such studies, the phenomenon will be understood, and, hopefully, a monitoring strategy will have been developed that could be used to monitor the effectiveness of countermeasure

Crucian, Brian↗

NASA NTRS2015

Microfluidic Device

Described herein are particular embodiments relating to a microfluidic device that may be utilized for cell sensing, counting, and/or sorting. Particular aspects relate to a microfabricated device that is capable of differentiating single cell types from dense cell populations. One particular embodiment relates a device and methods of using the same for sensing, counting, and/or sorting leukocytes from whole, undiluted blood samples.

Tai, Yu-Chong↗

NASA NTRS2016

Metabolomic and Genomic Markers of Atherosclerosis as Related to Oxidative Stress, Inflammation, and Vascular Function in Twin Astronauts

Background: Future human space travel will consist primarily of long-duration missions onboard the International Space Station (ISS) or exploration-class missions to Mars, its moons, or nearby asteroids. Astronauts participating in long-duration missions may be at an increased risk of oxidative stress and inflammatory damage due to radiation, psychological stress, altered physical activity, nutritional insufficiency, and hyperoxia during extravehicular activity. By studying one identical twin during his 1-year ISS mission and one ground-based twin, this work extends a current NASA-funded investigation to determine whether these spaceflight factors contribute to an accelerated progression of atherosclerosis. This study of twins affords a unique opportunity to examine the spaceflight-related atherosclerosis risk independent of the confounding factors associated with different genotypes. Purpose: The purpose of this investigation is to determine whether biomarkers of oxidative and inflammatory stress are elevated during and after long-duration spaceflight and determine if a relation exists between levels of these biomarkers and structural and functional indices of atherosclerotic risk measured in the carotid and brachial arteries. These physiological and biochemical data will be extended by using an exploratory approach to investigate the relationship between intermediate phenotypes and risk factors for atherosclerosis and the metabolomic signature from plasma and urine samples. Since metabolites are often the indirect products of gene expression, we will simultaneously assess gene expression and DNA methylation in leukocytes. Hypothesis: We predict that the space-flown twin will experience elevated biomarkers of oxidative stress and inflammatory damage, altered arterial structure and function, accelerated telomere shortening, dysregulation of genes associated with oxidative stress and inflammation, and a metabolic profile shift that is associated with elevated atherosclerosis risk factors. Conversely, these will not be observed in the ground-based twin. Methods: We will measure blood and urine biomarkers of oxidative stress and inflammation as well as arterial structure and function (carotid intima-medial thickness and brachial artery flow-mediated dilation) in one twin astronaut before, during, and after long-duration spaceflight and in his twin serving as a ground-based control. Furthermore, we will measure metabolomics (targeted and untargeted approaches) and genomic markers (DNA methylation, mRNA gene expression, telomere length) to elucidate the molecular mechanisms involved. A panel of biomarkers of oxidative and inflammatory stress will be measured in venous blood samples and 24-hour (in-flight) and 48-hour (pre- and post-flight) urine pools twice before flight, early (flight days 15 and 60) and late (2 weeks before landing) during the mission, and early in the post-flight recovery phase (approximately 3-5 days after landing). Arterial structure, assessed from measures of intima-media thickness, will be measured at the same times. Arterial function will be assessed using brachial flow-mediated dilation, a well-validated measure used to assess endothelium-dependent vasodilation and a sensitive predictor of atherosclerotic risk, only before and after spaceflight. Discussion: Pre- and in-flight data collection is in progress for the space-flown twin, and similar data have been obtained from the ground-based twin. Blood and urine samples will be batch processed when received from ISS after the conclusion of the 1-year mission. Results from these individual subjects will be compared to the larger complement of subjects participating in the companion study currently ongoing in ISS astronauts.

Lee, Stuart M. C.↗

NASA NTRS2016

Microfluidic Device

Tai, Yu-Chong↗

NASA NTRS2017

Metabolomic and Genomic Markers of Atherosclerosis as Related to Oxidative Stress, Inflammation, and Vascular Function in Twin Astronauts

BACKGROUND: Future human space travel will consist primarily of long-duration missions onboard the International Space Station (ISS) or exploration-class missions to Mars, its moons, or nearby asteroids. Astronauts participating in long-duration missions may be at an increased risk of oxidative stress and inflammatory damage due to radiation, psychological stress, altered physical activity, nutritional insufficiency, and hyperoxia during extravehicular activity. By studying one identical twin during his 1-year ISS mission and his ground-based twin, this work extends a current NASA-funded investigation to determine whether these spaceflight factors contribute to an accelerated progression of atherosclerosis. This study of twins affords a unique opportunity to examine spaceflight-related atherosclerosis risk that is independent of the confounding factors associated with different genotypes. PURPOSE: The purpose of this investigation was to determine whether biomarkers of oxidative and inflammatory stress are elevated during and after long-duration spaceflight and determine if a relation exists between levels of these biomarkers and structural and functional indices of atherosclerotic risk measured in the carotid and brachial arteries. These physiological and biochemical data will be extended by using an exploratory approach to investigate the relationship between intermediate phenotypes and risk factors for atherosclerosis and the metabolomic signature from plasma and urine samples. Since metabolites are often the indirect products of gene expression, we simultaneously assessed gene expression and DNA methylation in leukocytes. HYPOTHESIS: We predict that, compared to the ground-based twin, the space-flown twin will experience elevated biomarkers of oxidative stress and inflammatory damage, altered arterial structure and function, accelerated telomere shortening, dysregulation of genes associated with oxidative stress and inflammation, and a metabolic profile shift that is associated with elevated atherosclerosis risk factors. METHODS: In the space-flown twin, a panel of biomarkers of oxidative and inflammatory stress were measured in venous blood samples and in 24-h (in-flight) and 48-h (pre- and post-flight) urine pools collected twice before flight, six times during the mission (~FD15, 75, 180, 240, 300, 335), and early in the post-flight recovery phase (3-5 days after landing). We also measured metabolomic (targeted and untargeted approaches) and genomic markers (DNA methylation, mRNA gene expression, telomere length) in these samples. Arterial structure, assessed from measures of intima-media thickness, also were measured using standard clinical ultrasound at the same time points. Arterial function was assessed using brachial flow-mediated dilation, a well-validated measure used to assess endothelium-dependent vasodilation and a sensitive predictor of atherosclerotic risk, only before and after spaceflight. All of the same measures were obtained in the ground-based twin, but less frequently. DISCUSSION: All data collection has been completed for both the space-flown twin and the ground-based twin. Vascular structure and function measures have been analyzed, blood and urine samples have been batch-processed. Results from these individuals will be compared to each other, to data from other Twin Study investigations, and to the larger complement of subjects participating in the companion study currently ongoing in ISS astronauts.

Lee, Stuart M. C.↗

NASA NTRS2017

The Integrated Impact of Diet On Human Immune Response, the Gut Microbiota, and Nutritional Status During Adaptation to a Spaceflight Analog

Spaceflight impacts human physiology, including well documented immune system dysregulation. Diet, immune function, and the microbiome are interlinked, but diet is the only one of these factors that we have the ability to easily, and significantly, alter on Earth or during flight. As we understand dietary impacts on physiology more thoroughly, we may then improve the spaceflight diet to improve crew health and potentially reduce flight-associated physiological alterations. It is expected that increasing the consumption of fruits and vegetables and bioactive compounds (e.g.,omega-3 fatty acids, lycopene, flavonoids) and therefore enhancing overall nutritional intake from the nominal shelf-stable, fully-processed space food system could serve as a countermeasure to improve human immunological profiles, the taxonomic profile of the gut microbiota, and nutritional status, especially where currently dysregulated during spaceflight. This interdisciplinary study will determine the effect of the current shelf-stable spaceflight diet compared to an "enhanced" shelf-stable spaceflight diet (25% more foods rich in omega-3 fatty acids, lycopene, flavonoids, fruits, and vegetables). The NASA Human Exploration Research Analog (HERA) 2017 missions, consisting of closed chamber confinement, realistic mission simulation, in a high-fidelity mock space vehicle, will serve as a platform to replicate mission stressors and the dysregulated physiology observed in astronauts. Biosampling of crew members will occur at selected intervals, with complete dietary tracking. Outcome measures will include immune markers (e.g., peripheral leukocyte distribution, inflammatory cytokine profiles, T cell function), the taxonomic and metatranscriptomic profile of the gut microbiome, and nutritional status biomarkers and metabolites. Data collection will also include complete dietary tracking. Statistical evaluations will determine physiological and biochemical shifts in relation to nutrient in take and study phase. Beneficial improvements will provide evidence of the impact of diet on crew health and adaptation to this spaceflight analog, and will aid in the design and development of more-efficient targeted dietary interventions.

Douglas, G. L.↗

NASA NTRS2017

Microfluidic Device

Tai, Yu-Chong↗

NASA NTRS2018

The Integrated Impact of Diet on Human Immune Response, the Gut Microbiota, and Nutritional Status During Adaptation to a Spaceflight Analog

Spaceflight impacts human physiology, including well documented immune system dysregulation. Diet, immune function, and the microbiome are interlinked, but diet is the only one of these factors that we have the ability to easily, and significantly, alter on Earth or during flight. As we understand dietary impacts on physiology more thoroughly, we may then improve the spaceflight diet to improve crew health and potentially reduce spaceflight-associated physiological alterations. It is expected that increasing the consumption of fruits and vegetables and bioactive compounds (e.g., omega-3 fatty acids, lycopene, flavonoids) and therefore enhancing overall nutritional intake from the nominal shelf-stable, fully-processed space food system could serve as a countermeasure to improve human immunological profiles, the taxonomic profile of the gut microbiota, and nutritional status, especially where currently dysregulated during spaceflight. This interdisciplinary study will determine the effect of the current shelf-stable spaceflight diet compared to an "enhanced" shelf-stable spaceflight diet (25% more foods rich in omega-3 fatty acids, lycopene, flavonoids, and more fruits, and vegetables in general). The NASA Human Exploration Research Analog (HERA) 2017 missions, consisting of four 45-day missions with closed chamber confinement and realistic mission simulation in a high-fidelity mock space vehicle, will serve as a platform to replicate mission stressors and the effects on crew biochemistry, immunology, and the gut microbiome. Bio sampling of crewmembers is scheduled for selected intervals pre- and in-mission. Data collection also includes dietary intake recording. Outcome measures will include immune markers (e.g., peripheral leukocyte distribution, inflammatory cytokine profiles, T cell function), the taxonomic and metatranscriptomic profile of the gut microbiome, and nutritional status biomarkers and metabolites. Statistical evaluations will determine physiological and biochemical shifts in relation to nutrient intake and study phase. To date, sample collection has been completed for 2 crewmembers from the first mission, aka Campaign 4 Mission 1. Mission 2 was terminated after 22 days due to effects of Hurricane Harvey, and sample collection was not completed. Sample collection will continue for Campaign 4 Mission 3 and 4 prior to comprehensive sample analysis. Beneficial improvements will provide evidence of the impact of diet on crew health and adaptation to this spaceflight analog, and will aid in the design and development of more-efficient targeted dietary interventions for exploration missions.

Douglas, G. L.↗

NASA NTRS2017

Microfluidic Device

Tai, Yu-Chong↗

NASA NTRS2019

Modeled Microgravity Induces Neutrophil Extracellular Trap (NET)osis Formation and Reduced Phagocytosis of Polymorphonuclear Neutrophils

Spaceflight can dysregulate immunity, by way of increasing granulocytes numbers with impaired function. Polymorphonuclear neutrophils (PMN) are granulocytes that are first responders to infection or injury, and consist of the largest pool of immune cells in humans. PMNs function during innate immunity, through phagocytosis and promotion of inflammation, via the release of reactive oxygen species (ROS) mediators and granule-containing enzymes, such as myeloperoxidase (MPO) and NADPH oxidase-2 (NOX-2). In addition, neutrophil extracellular trap (NET) formation is another mechanism of PMN surveillance that works independently of engulfment phagocytosis, and is a last resort function that can induce NETosis or PMN-specific cell death. Previous studies in our lab have identified increased mature neutrophils, ROS and MPO production, and reduced phagocytosis in granulocytes in simulated microgravity (sug) models of hindlimb unloading (HU) in adult mice and leukocytes cultured in high-aspect rotating wall vessels (HARV-RWV). Since sug impaired phagocytosis, but improved enzymatic mediator production of MPO and redox molecules, we sought to address the third known function of PMNs, NETosis. For this, PMNs were culture in the presence or absence of the anti-oxidant N-acetyl cysteine (NAC), which rescued impaired phagocytosis that was present in sug without NAC treatment. Further, NETosis was induced in sug that was no different in the presence of NAC, suggesting NAC targets independent functions of PMNs under sug. Collectively, these results suggest modeled microgravity induced NETosis, which opens a new avenue for spaceflight studies in immune dysfunction.

Paul, Amber M.↗