Genetic Ancestry May Determine Immune Response to Influenza

Investigators from the University of Chicago have long been interested in understanding how influenza infection affects individuals with different genetic ancestry. In a study published this week in Science, they explored how various cell types respond to viral infection.

The investigators used single-cell RNA-sequencing to analyze gene expression patterns in peripheral mononuclear blood cells. The cells, collected from men of European or African ancestry, were exposed to the flu in a laboratory setting.

The investigators examined the gene expression signatures of various immune cell types to determine how each cell type’s gene expression was affected by influenza infection. 

The blood cells from individuals with European ancestry demonstrated an increase in type 1 interferon pathway activity during early influenza infection. This elevated pathway activation was correlated with greater capability to hinder virus replication.

Luis Barreiro, PhD, the study’s senior author and an associate professor of medicine at UChicago, said, “Interferons are proteins that are critical for fighting viral infections...Inducing a strong type I interferon pathway response early upon infection stops the virus from replicating and may therefore have a direct impact on the body’s ability to control the virus.”

Barreiro noted, “Unexpectedly, this central pathway to our defense against viruses appears to be amongst the most divergent between individuals from African and European ancestry.”

The study authors pointed out that this difference in immune pathway activation could be a cause of influenza disparities across racial groups, such as non-Hispanic Black Americans being the most likely to be hospitalized due to the flu.

However, they emphasized that these results are not proof of genetic differences in disease susceptibility, but rather of differing environmental and lifestyle factors among racial groups that could influence gene expression and alter immune response.

Barreiro said, “There’s a strong relationship between the interferon response and the proportion of the genome that is of African ancestry, which might make you think it’s genetic, but it’s not that simple. Genetic ancestry also correlates with environmental differences. A lot of what we’re capturing could be the result of other disparities in our society, such as systemic racism and healthcare inequities. Although some of the differences we show in the paper can be linked to specific genetic variation, showing that genetics do play some role, such genetic differences are not enough to fully explain the differences in the interferon response.”