Immunization Induces Inflammation in the Mouse Heart During Spaceflight

Overview

Journal BMC Genomics

Publisher Biomed Central

Specialty Genetics

Date 2025 Mar 11

PMID 40065216

Authors

Alicia L Veliz

Lorelei Hughes

Delia Carrillo

Michael J Pecaut

Mary Kearns-Jonker

Affiliations

Soon will be listed here.

Abstract

Space travel is a growing area of interest and includes initiatives such as NASA's Moon-to-Mars Mission. Reports on the cardiovascular effects of space travel reveal changes in morphology, metabolism, and function of the cardiovascular system. In this study, the cardiovascular response to immunization in space was studied in mice which were housed and immunized while on the International Space Station (ISS). Mice were immunized with tetanus toxoid combined with the adjuvant CpG (TT + CpG) and the effects of vaccination in space were studied using transcriptomics. Analysis of the mouse heart transcriptome was performed on flight control and flight-immunized mice. The results show that immunization aboard the ISS stimulates heightened inflammation in the heart via induction of the nuclear factor kappa B (NF-κB) signaling pathway to promote the release of the pro-inflammatory cytokines IFNγ, IL-17 and IL-6. Additional transcriptomic changes included alterations in the cytoskeleton and in the expression of transcripts associated with protection from oxidative stress. In summary, inflammation in the heart can occur following immunization in space. This investigation explores the impact of immune challenges on the heart and lays the groundwork for future research into additional cardiac alterations which can occur during spaceflight.

References

Sherman B, Hao M, Qiu J, Jiao X, Baseler M, Lane H . DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res. 2022; 50(W1):W216-W221. PMC: 9252805. DOI: 10.1093/nar/gkac194. View

Montgomery J, Ryan M, Engler R, Hoffman D, McClenathan B, Collins L . Myocarditis Following Immunization With mRNA COVID-19 Vaccines in Members of the US Military. JAMA Cardiol. 2021; 6(10):1202-1206. PMC: 8243257. DOI: 10.1001/jamacardio.2021.2833. View

Miller B, Hoffman N, Merali S, Zhang X, Wang J, Rajan S . TRPM2 channels protect against cardiac ischemia-reperfusion injury: role of mitochondria. J Biol Chem. 2014; 289(11):7615-29. PMC: 3953274. DOI: 10.1074/jbc.M113.533851. View

Ninh V, Brown J . The contribution of the cardiomyocyte to tissue inflammation in cardiomyopathies. Curr Opin Physiol. 2022; 19:129-134. PMC: 8730355. DOI: 10.1016/j.cophys.2020.10.003. View

Krittanawong C, Isath A, Kaplin S, Virk H, Fogg S, Wang Z . Cardiovascular disease in space: A systematic review. Prog Cardiovasc Dis. 2023; 81:33-41. DOI: 10.1016/j.pcad.2023.07.009. View

Martinez-Espinoza I, Guerrero-Plata A . The Relevance of TLR8 in Viral Infections. Pathogens. 2022; 11(2). PMC: 8877508. DOI: 10.3390/pathogens11020134. View

Yu Y, Yan Y, Niu F, Wang Y, Chen X, Su G . Ferroptosis: a cell death connecting oxidative stress, inflammation and cardiovascular diseases. Cell Death Discov. 2021; 7(1):193. PMC: 8313570. DOI: 10.1038/s41420-021-00579-w. View

Sequeira V, Nijenkamp L, Regan J, van der Velden J . The physiological role of cardiac cytoskeleton and its alterations in heart failure. Biochim Biophys Acta. 2013; 1838(2):700-22. DOI: 10.1016/j.bbamem.2013.07.011. View

Fonseca F, Izar M . Role of Inflammation in Cardiac Remodeling After Acute Myocardial Infarction. Front Physiol. 2022; 13:927163. PMC: 9274081. DOI: 10.3389/fphys.2022.927163. View

10.

Kim H, Jenista E, Wendell D, Azevedo C, Campbell M, Darty S . Patients With Acute Myocarditis Following mRNA COVID-19 Vaccination. JAMA Cardiol. 2021; 6(10):1196-1201. PMC: 8243258. DOI: 10.1001/jamacardio.2021.2828. View

11.

Huber J, Farrar J . Regulation of effector and memory T-cell functions by type I interferon. Immunology. 2011; 132(4):466-74. PMC: 3075500. DOI: 10.1111/j.1365-2567.2011.03412.x. View

12.

Cogoli A . The effect of hypogravity and hypergravity on cells of the immune system. J Leukoc Biol. 1993; 54(3):259-68. DOI: 10.1002/jlb.54.3.259. View

13.

Wilke A, Schonian U, Herzum M, Hengstenberg C, HUFNAGEL G, Brilla C . [The extracellular matrix and cytoskeleton of the myocardium in cardiac inflammatory reaction]. Herz. 1995; 20(2):95-108. View

14.

Willerson J, Ridker P . Inflammation as a cardiovascular risk factor. Circulation. 2004; 109(21 Suppl 1):II2-10. DOI: 10.1161/01.CIR.0000129535.04194.38. View

15.

Juhl 4th O, Buettmann E, Friedman M, DeNapoli R, Hoppock G, Donahue H . Update on the effects of microgravity on the musculoskeletal system. NPJ Microgravity. 2021; 7(1):28. PMC: 8302614. DOI: 10.1038/s41526-021-00158-4. View

16.

Rao X, Huang X, Zhou Z, Lin X . An improvement of the 2ˆ(-delta delta CT) method for quantitative real-time polymerase chain reaction data analysis. Biostat Bioinforma Biomath. 2015; 3(3):71-85. PMC: 4280562. View

17.

Smith J . IL-6 and the dysregulation of immune, bone, muscle, and metabolic homeostasis during spaceflight. NPJ Microgravity. 2018; 4:24. PMC: 6279793. DOI: 10.1038/s41526-018-0057-9. View

18.

Huang D, Sherman B, Lempicki R . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009; 4(1):44-57. DOI: 10.1038/nprot.2008.211. View

19.

Boyd J, Mathur S, Wang Y, Bateman R, Walley K . Toll-like receptor stimulation in cardiomyoctes decreases contractility and initiates an NF-kappaB dependent inflammatory response. Cardiovasc Res. 2006; 72(3):384-93. DOI: 10.1016/j.cardiores.2006.09.011. View

20.

Hashemi B, Penkala J, Vens C, Huls H, Cubbage M, Sams C . T cell activation responses are differentially regulated during clinorotation and in spaceflight. FASEB J. 1999; 13(14):2071-82. DOI: 10.1096/fasebj.13.14.2071. View