[en] Early life adversity (ELA) is associated with a higher risk for chronic and noncommunicable diseases in adulthood. Changes in the HPA axis and the immune system have been proposed to underlie this association, however current ELA research remains mainly focused on neglect, abuse and low socioeconomic status as sources of childhood adversity.
Early-life adversity covers a range of physical, social and environmental stressors. Acute viral infections in early life are a major source of such adversity and have been associated with a broad spectrum of later-life effects outside the immune system or “off-target”. These include an altered hypothalamus-pituitary-adrenal axis and metabolic reactions.
Here, we used a murine postnatal day 14 (PND 14) Influenza A (H1N1) infection model and applied a semi-holistic approach including phenotypic measurements, gene expression arrays and diffusion neuroimaging techniques to investigate HPA axis dysregulation, energy metabolism, brain connectivity, microbial composition and immune cell shift .
We then extended our mouse model for a postnatal day 56 (PND56) viral challenge to study immune reactivation after an early life “priming” event. We could show that an early life influenza A virus infection led to an immediate shift in lung microbiota and long-term changes in gut microbiome composition. We also observed several sex-specific effects: retarded growth of males, baseline blood glucose levels being increased in females and decreased in males, and baseline corticosterone levels were reduced while total number of CD3+ cells were higher in males. At the same time, we found a microbial composition shift persistent several weeks after the early life infection. For the brain, MRI scans identified reduced connectivity in the cortex, midbrain and cerebellum which were accompanied by tissue-specific gene expression signatures.
Early-life infection appeared to have independently affected each of the systems, potentially independent of HPA axis or immune perturbations.
Research center :
LIH - Luxembourg Institute of Health
Life sciences: Multidisciplinary, general & others
Author, co-author :
Merz, Myriam Pia ; University of Luxembourg > Faculty of Science, Technology and Medecine (FSTM)
A TALE OF ADVERSITY: THE IMPACT OF EARLY LIFE INFECTION BEYOND THE IMMUNE SYSTEM
Defense date :
20 January 2022
Number of pages :
Unilu - University of Luxembourg, Esch-sur-Alzette, Luxembourg