| Description |
Exposure to low-pressure hypoxia in high-altitude mountaineering induces a series of physiologic, metabolic, and immunologic changes. In this study, we performed a longitudinal multi-omics analysis of 55 blood samples from 11 mountaineers during two phases of mountaineering (habituation phase and very high altitude climbing phase). Our comprehensive analyses included metabolomic and lipidomic analyses of plasma and single-cell transcriptomic analyses of 375,722 immune cells. Longitudinal analyses revealed dynamic immune response changes, which during the habituation period were characterized by a down-regulation of the inflammatory response in monocytes and classical dendritic cells (cDCs) and an increase in the proportion of cytotoxic CD8+ T cells, accompanied by an enhancement of their immune effector processes. In contrast, during extreme high-altitude mountaineering, the inflammatory response was activated and T cell effector functions were impaired, accompanied by enhanced cellular responses to hypoxia and oxidative stress pathways. Furthermore, we found an up-regulation of glycolytic and antioxidant gene expression during extreme high-altitude mountaineering, which was mainly coordinated by HIF1A and NFE2L2, whereas a reduction in the expression of these genes was observed in dysregulated plasmacytoid dendritic cells (pDCs). Finally, high-resolution plasma metabolic analysis revealed significant changes in climbers' metabolism, including enhanced glutamine and fatty acid metabolism. |
