Individuals of African Ancestry respond more strongly to pathogen than Individuals of European Ancestry

by Jalwa Afroz ’17

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Figure 1. A recent study shows African ancestry is associated with a stronger inflammatory immune response.

 

The human immune system, varying amongst individuals from different populations, evolved under selective pressure from pathogenic environments. Genome-wide association studies (GWAS) have shown extreme differences in allele frequency between various human populations for infectious, autoimmune, and inflammatory diseases. Additionally, expression quantitative trait locus (eQTL) mapping studies in antigen-exposed immune cells have identified hundreds of genetic variants that also explain variation in immune responses. However, these studies have mostly focused on European-ancestry populations, without clarifying the inter-population variations in immune responses.

Dr. Luis Barreiro and his colleagues used an RNA-sequencing based immune response eQTL study to test for the degree to which innate immune responses are different, genetic variants, and evolutionary mechanisms between European and African-ancestral populations. Phagocytic cells that are essential for fighting foreign invaders, tissue development, and homeostasis were derived from 80 African American and 95 European American individuals. These phagocytic cells were infected with either Listeria monocytogenes gram-positive bacteria or Salmonella typhimurium gram-negative bacteria. After two hours, 171 individuals with RNA-sequencing data were collected and each individual was genotyped for over 4.6 million single nucleotide polymorphisms (SNPs).

Many self-identified African-American individuals had a high proportion of European ancestry (an average of 30%), whereas European-Americans had about 0.4% African admixture. Barreiro and colleagues discovered that macrophages of individuals from African descent had a higher, stronger transcriptional increase in ancestry-related expressed genes to bacterial infections. These genes were also enriched for inflammatory response, cytokine production, T cell activation, and apoptosis. In addition, the number of bacteria in the macrophages of individuals with high levels of African ancestry was 3.2 times lower than those of European ancestry.

As human populations moved out of Africa, they were exposed to lower pathogen levels, which could have reduced the need for strong pro-inflammatory signals. The data generated in this study is accessible to the public, which enables easy querying and visualization of ancestry-related transcriptional differences. This could be used as a resource in the continued quest to understand pathogen-associated human diversity.

References:

  1. Y. Nedelec, et al., Genetic ancestry and natural selection drive population differences in immune responses to pathogen. Cell 167, 657-669 (2016).
  2. Image acquired from: http://www.theroot.com/articles/history/2014/02/traces_of_african_ancestry_in_a_white_person_the_likely_reason/
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