Modelling of early-life immunity shaped by contrasting environments 2256917

Abstract Introduction The neonatal period represents a critical window of immune development, during which environmental exposures influence health long term. Prior data capturing immune maturation in human newborns are limited to date. This multicohort study involves 1,000 infants across contrasting environmental contexts including rural African and urban European regions to map early-life immune trajectories and identify exposure-dependent variation. Methods Peripheral whole blood samples are collected longitudinally during the first years of life. Spectral flow cytometry and mass cytometry is used to study immune cell composition and functional maturation, while targeted plasma proteomics quantifies key soluble proteins. Metadata on key clinical and biometric features as well as health outcomes complement the analysis. Integrated computational modelling combines trajectory inference and modeling to reconstruct immune development and link molecular signatures to health endpoints. Results High-dimensional profiling reveals substantial location-dependent heterogeneity in early immune trajectories. Conserved maturation patterns are identified across cohorts, alongside exposure-dependent deviations. Early-life factors–such as perinatal antibiotic exposure–are associated with persistent shifts in cellular profiles. Multimodal models predict exposure status and early health outcomes, highlighting coordinated maturation of different immune modules shaped by the environment. Conclusion This large-scale longitudinal study provides a multidimensional view of human neonatal immune development. By integrating cellular, proteomic, and contextual data, it delineates conserved and modifiable features of immune ontogeny. The findings demonstrate how early exposures can reshape developmental trajectories, offering a foundation for predictive and preventive strategies that promote healthy immune maturation in early life. Funding Source German research council postdoc stipend Topic Categories Immune Mechanisms of Human Disease (HUM)