Geography influences early programming of the immune system

By Sarah Anderson, PhD

An international team of researchers has found that programming of the immune system in the first seven days of life occurs uniquely in separate geographic cohorts of newborns.

Their study, published in Nature Communications, reveals that a core immune development trajectory in humans is overlaid with population-specific differences.

“These differences are frequently involved in response to infections and could be used to predict susceptibility and response to infection throughout the first year of life,” said Dr. Bob Hancock, a professor in the Department of Microbiology and Immunology at UBC and senior author of the study.  

Immune programming throughout the first week of life is an important determinant of health during infancy, a period when one is especially vulnerable to infection. Strategies to reduce infant morbidity and mortality hinge upon a nuanced understanding of early life immune development. 

Dr. Hancock’s team previously studied these pathways in newborns and found that the first steps in maturing the immune system follow a robust and highly regulated process. 

In the new study, the researchers dived deeper into common versus population-specific threads of immune programming, comparing two distinct cohorts of newborns from The Gambia and Papua New Guinea. “The major burden of infectious diseases in early life occurs in developing countries, impacting both survival and subsequent quality of life,” said Dr. Hancock. 

Through the Expanded Program on Immunization Consortium, clinical-facing researchers obtained consent from mothers to collect blood samples from 90 newborns at several timepoint throughout their first week of life. Aliquots from these samples were transported to UBC, where Dr. Hancock’s team analyzed to what degree the activity of each gene was turned up or down.

This gene expression data revealed that key immune developmental milestones unfolded consistently, with 88 to 96 percent of the immunological blueprint being shared between the two cohorts. However, a set of approximately 600 genes showed differences in expression between the two populations, including genes involved in recognizing and clearing foreign substances and other processes related to susceptibility to infection. Many of the genes also instructed the cell to make “hub” proteins that receive and transmit signals between a larger network of interconnected proteins. 

These findings indicate that certain immune pathways were wired differently in each of the two groups, which may be attributed to genetics and/or epigenetics (how environment and lifestyle affect the way genes work). 

“Our results suggest that we can extrapolate the core immune development program to all newborns, but that there is an important set of genes for which expression varies, which must be analyzed in the specific population of interest,” said Dr. Hancock. 

In future studies, the researchers aim to link these differences in gene expression to clinical outcomes such as susceptibility to infection and protection from vaccines, providing a tool that could be used to predict responses to immune challenges and tailor interventions accordingly. They also plan to collect data on maternal infection history and vaccination status and to explore how these factors influence neonatal immune development.

Ultimately, Dr. Hancock said, “We hope to establish a better understanding of and appreciation for the incredibly profound and complex alterations that occur in newborns in the vital first week of life.”