{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T11:12:34Z","timestamp":1783941154390,"version":"3.55.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The present era of spaceflight is accompanied by two meaningful breakthroughs. The access to in-orbit missions for civilians and the increasing enrolment of female astronauts require detailed investigations on the impact of gravitational stress on human physiology with focus on sex-specific differences. To assess the responsive capacities of innate and adaptive immunity in this context, functional characterizations were performed in women and men in a parabolic flight study. Blood and saliva were collected 1 month prior and on the day before the flight, as well as directly after flight and on the following day. Leukocyte proportions were quantified, and NETosis as well as phagocytic activity was tested. The impact of gravitational stress on the ability to mount a functional immune response was examined by a 6-h whole-blood incubation assay with subsequent analysis of leukocyte surface activation marker expression and cytokine secretion. Parabolic flight induced a temporary increase in granulocyte proportions, which however did not influence NETosis and phagocytosis. Throughout the flight week, leukocyte activation and cytokine secretion patterns remained unaltered in response to antigen stimulation. No differences were found regarding the direction or intensity of immune response either in women or in men. However, when comparing effects 1 month before flight and the flight week, immune responses were still present but remarkably weaker during flight week, which was independent of cortisol levels. Altogether, this study elicited two important findings. Firstly, no sex-specific increased risk exists for immune dysregulation by acute gravitational stress. Secondly, merely changing the day to day surrounding dampens crucial immune responses, which requires further investigations.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1673072","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T05:16:15Z","timestamp":1763356575000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Biological sex as a variable in immunity does not affect parabolic flight-induced alterations in immune responses"],"prefix":"10.3389","volume":"16","author":[{"given":"Dominique","family":"Moser","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith-Irina","family":"Buchheim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Biere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Matzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"D\u00b4Amico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Chouk\u00e9r","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Woehrle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Feuerecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"key":"B1","unstructured":"Space A\n          \n          \n          2025"},{"key":"B2","unstructured":"NASA\n          \n          \n          2025"},{"key":"B3","unstructured":"4 I\n          \n          \n          2025"},{"key":"B4","unstructured":"Dawn P\n          \n          \n          2025"},{"key":"B5","unstructured":"SPACEX\n          \n          \n          2025"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/cells12010040","article-title":"Human health during space travel: state-of-the-art review","volume":"12","author":"Krittanawong","year":"2022","journal-title":"Cells"},{"key":"B7","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1038\/s41526-024-00452-x","article-title":"Hypergravity is more challenging than microgravity for the human sensorimotor system","volume":"11","author":"Chomienne","year":"2025","journal-title":"NPJ Microgravity"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/s00221-023-06677-8","article-title":"Under pressure-the influence of hypergravity on electrocortical activity and neurocognitive performance","volume":"241","author":"Badal\u00ec","year":"2023","journal-title":"Exp Brain Res"},{"key":"B9","doi-asserted-by":"publisher","first-page":"6614","DOI":"10.1038\/s41598-019-42829-z","article-title":"Hypergravity and microgravity exhibited reversal effects on the bone and muscle mass in mice","volume":"9","author":"Tominari","year":"2019","journal-title":"Sci Rep"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.952723","article-title":"The application of artificial gravity in medicine and space","volume":"13","author":"Isasi","year":"2022","journal-title":"Front Physiol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00085","article-title":"Stress related shift toward inflammaging in cosmonauts after long-duration space flight","volume":"10","author":"Buchheim","year":"2019","journal-title":"Front Physiol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.2147\/IJGM.S114188","article-title":"Incidence of clinical symptoms during long-duration orbital spaceflight","volume":"9","author":"Crucian","year":"2016","journal-title":"Int J Gen Med"},{"key":"B13","doi-asserted-by":"publisher","first-page":"S198","DOI":"10.4103\/0028-3886.259125","article-title":"Effects of microgravity and other space stressors in immunosuppression and viral reactivation with potential nervous system involvement","volume":"67","author":"Mann","year":"2019","journal-title":"Neurol India"},{"key":"B14","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1186\/1478-811X-11-98","article-title":"The oxidative burst reaction in mammalian cells depends on gravity","volume":"11","author":"Adrian","year":"2013","journal-title":"Cell Commun Signal"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01046.2015","article-title":"Parabolic flight as a spaceflight analog","volume":"120","author":"Shelhamer","year":"2016","journal-title":"J Appl Physiol (1985)"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s12217-015-9458-5","article-title":"Simulating Parabolic Flight like g-Profiles on Ground - A Combination of Centrifuge and Clinostat","volume":"28","author":"Brungs","year":"2016","journal-title":"Microgravity Sci Technol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.2009.02136.x","article-title":"Parabolic flight primes cytotoxic capabilities of polymorphonuclear leucocytes in humans","volume":"39","author":"Kaufmann","year":"2009","journal-title":"Eur J Clin Invest"},{"key":"B18","doi-asserted-by":"publisher","first-page":"11276","DOI":"10.1038\/s41598-019-47655-x","article-title":"Cells\u00b4 Flow and Immune Cell Priming under alternating g-forces in Parabolic Flight","volume":"9","author":"Moser","year":"2019","journal-title":"Sci Rep"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1089\/jwh.2014.4913","article-title":"Effects of sex and gender on adaptation to space: immune system","volume":"23","author":"Kennedy","year":"2014","journal-title":"J Womens Health (Larchmt)"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.90","article-title":"Sex differences in immune responses","volume":"16","author":"Klein","year":"2016","journal-title":"Nat Rev Immunol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s13293-019-0231-0","article-title":"Sex differences in stress and immune responses during confinement in Antarctica","volume":"10","author":"Strewe","year":"2019","journal-title":"Biol Sex Differ"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-018-00728-x","article-title":"Sex differences in immunity","volume":"41","author":"Lotter","year":"2019","journal-title":"Semin Immunopathol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.281053","article-title":"World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects","volume":"310","year":"2013","journal-title":"JAMA"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01076","article-title":"Editorial: sex hormones and gender differences in immune responses","volume":"10","author":"Ortona","year":"2019","journal-title":"Front Immunol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1038\/s41577-024-00996-9","article-title":"The conneXion between sex and immune responses","volume":"24","author":"Forsyth","year":"2024","journal-title":"Nat Rev Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.564950","article-title":"Neutrophil-to-lymphocyte ratio: A biomarker to monitor the immune status of astronauts","volume":"11","author":"Paul","year":"2020","journal-title":"Front Immunol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.952928","article-title":"Long-duration head-down tilt bed rest confirms the relevance of the neutrophil to lymphocyte ratio and suggests coupling it with the platelet to lymphocyte ratio to monitor the immune health of astronauts","volume":"13","author":"Jacob","year":"2022","journal-title":"Front Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0206272","article-title":"Gravitational stress during parabolic flights reduces the number of circulating innate and adaptive leukocyte subsets in human blood","volume":"13","author":"Stervbo","year":"2018","journal-title":"PloS One"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1097\/MS9.0000000000003304","article-title":"Stress, neutrophils, and immunity: a dynamic interplay","volume":"87","author":"Obeagu","year":"2025","journal-title":"Ann Med Surg (Lond)"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00381.2013","article-title":"Five days of head-down-tilt bed rest induces noninflammatory shedding of L-selectin","volume":"115","author":"Feuerecker","year":"2013","journal-title":"J Appl Physiol (1985)"},{"key":"B31","doi-asserted-by":"publisher","first-page":"8376","DOI":"10.1038\/s41598-021-87790-y","article-title":"Scopolamine promotes neuroinflammation and delirium-like neuropsychiatric disorder in mice","volume":"11","author":"Cheon","year":"2021","journal-title":"Sci Rep"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1115721","article-title":"Anticholinergic effect of resveratrol with vitamin E on scopolamine-induced Alzheimer\u2019s disease in rats: Mechanistic approach to prevent inflammation","volume":"14","author":"Foudah","year":"2023","journal-title":"Front Pharmacol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-022-01071-2","article-title":"Minocycline attenuates cholinergic dysfunction and neuro-inflammation-mediated cognitive impairment in scopolamine-induced Alzheimer\u2019s rat model","volume":"30","author":"Amirahmadi","year":"2022","journal-title":"Inflammopharmacology"},{"key":"B34","doi-asserted-by":"publisher","first-page":"106240","DOI":"10.1016\/j.ejps.2022.106240","article-title":"Corrigendum to \u2018The effects of scopolamina on the survival time and microcirculation of septic shock rats\u2019[Eur J Pharm Sci. 141 (2020)105062","volume":"175","author":"Song","year":"2022","journal-title":"Eur J Pharm Sci"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1159\/000373930","article-title":"Signal transduction in primary human T lymphocytes in altered gravity during parabolic flight and clinostat experiments","volume":"35","author":"Tauber","year":"2015","journal-title":"Cell Physiol Biochem"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1084\/jem.178.2.669","article-title":"CD40 expression by human monocytes: regulation by cytokines and activation of monocytes by the ligand for CD40","volume":"178","author":"Alderson","year":"1993","journal-title":"J Exp Med"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1999","DOI":"10.1084\/jem.180.5.1999","article-title":"Triggering of human monocyte activation through CD69, a member of the natural killer cell gene complex family of signal transducing receptors","volume":"180","author":"De Maria","year":"1994","journal-title":"J Exp Med"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021014894","article-title":"HbS promotes TLR4-mediated monocyte activation and proinflammatory cytokine production in sickle cell disease","volume":"140","author":"Allali","year":"2022","journal-title":"Blood"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2008.07.076","article-title":"Evaluation of CD86\/CD28 and CD40\/CD154 pathways in regulating monocyte-derived CD80 expression during their interaction with allogeneic endothelium","volume":"40","author":"Wang","year":"2008","journal-title":"Transplant Proc"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000254724.54515.2F","article-title":"Reduced monocyte CD86 expression in postinflammatory immunodeficiency","volume":"35","author":"Wolk","year":"2007","journal-title":"Crit Care Med"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/375603a0","article-title":"Antigen presentation mediated by recycling of surface HLA-DR molecules","volume":"375","author":"Pinet","year":"1995","journal-title":"Nature"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2005.03.014","article-title":"Stress hormones in health and illness: the roles of work and gender","volume":"30","author":"Lundberg","year":"2005","journal-title":"Psychoneuroendocrinology"},{"key":"B43","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1093\/intimm\/dxy001","article-title":"Oxidative burst and Dectin-1-triggered phagocytosis affected by norepinephrine and endocannabinoids: implications for fungal clearance under stress","volume":"30","author":"Buchheim","year":"2018","journal-title":"Int Immunol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(99)00219-X","article-title":"Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder","volume":"46","author":"Southwick","year":"1999","journal-title":"Biol Psychiatry"},{"key":"B45","doi-asserted-by":"publisher","first-page":"104587","DOI":"10.1016\/j.yhbeh.2019.104587","article-title":"Cortisol response to stress: The role of expectancy and anticipatory stress regulation","volume":"117","author":"Pulopulos","year":"2020","journal-title":"Horm Behav"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsycho.2012.08.003","article-title":"Differential effects of mild chronic stress on cortisol and S-IgA responses to an acute stressor","volume":"91","author":"Viena","year":"2012","journal-title":"Biol Psychol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1097\/00006842-200011000-00010","article-title":"Chronic stress modulates the immune response to a pneumococcal pneumonia vaccine","volume":"62","author":"Glaser","year":"2000","journal-title":"Psychosom Med"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1159\/000216188","article-title":"Enhancing versus suppressive effects of stress on immune function: implications for immunoprotection and immunopathology","volume":"16","author":"Dhabhar","year":"2009","journal-title":"Neuroimmunomodulation"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-psych-010213-115205","article-title":"Why sleep is important for health: a psychoneuroimmunology perspective","volume":"66","author":"Irwin","year":"2015","journal-title":"Annu Rev Psychol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00010.2018","article-title":"The sleep-immune crosstalk in health and disease","volume":"99","author":"Besedovsky","year":"2019","journal-title":"Physiol Rev"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abm2465","article-title":"The circadian immune system","volume":"7","author":"Wang","year":"2022","journal-title":"Sci Immunol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010752","article-title":"Motion sickness, stress and the endocannabinoid system","volume":"5","author":"Chouk\u00e8r","year":"2010","journal-title":"PLoS One"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1673072\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T05:16:16Z","timestamp":1763356576000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1673072\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,17]]},"references-count":52,"alternative-id":["10.3389\/fimmu.2025.1673072"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1673072","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,17]]},"article-number":"1673072"}}