Europeans have weaker immune systems than Africans, in part because of Neanderthal DNA

A new study finds that Europeans are more likely to develop infections, while Africans are more susceptible to autoimmune inflammatory diseases.

A study released today in Cell has found that Africans have a stronger immune response to infection when compared to Europeans, in part because early Europeans interbred with Neanderthals. We talked to lead author Lluis Quintana-Murci of Institut Pasteur and CNRS in Paris to find out why there are both positives and negatives to having a weaker immune system. 

ResearchGate: Could you briefly explain the findings of your study and their significance?

Lluis Quintana-Murci: Our findings show that population differences in transcriptional immune responses are widespread, and that they are mainly accounted for by genetic variants that differ in their frequencies between human populations. Natural selection has favored such population differences, highlighting genetic adaptation to local pathogenic environments. Finally, we found that interbreeding with Neanderthals has been an additional source of genetic innovation in early European populations and has played a role in shaping their immune responses.

RG: Could you explain the method you used to reach these results?

Quintana-Murci: We compared the transcriptional responses (by RNA sequencing) of monocytes from individuals of European and African ancestry to different immune stimulation, mimicking bacterial and viral challenges and the influenza virus. We then studied the genetic profiles of all individuals in order to determine to which extent genetics control the immune response to infection.

RG: What did you expect to find?

Quintana-Murci: Actually, we did not have a priori of the extent to which Africans and Europeans would differ in their immune responses. We were surprised by some findings. First, that a single variant in the TLR1 gene could explain such a high proportion of differences in inflammatory responses to bacterial stimuli between Europeans and Africans, knowing that previous studies demonstrated that the same genetic variant was a target of selection in Europeans. This strongly suggests that a diminished inflammatory response has conferred a selective advantage to European populations. Second, we were surprised to find that Europeans had “borrowed” regulatory variants from Neanderthals, particularly variants regulating transcriptional responses to viral changes.

RG: You mention that it would appear that European populations have been selected to display reduced immune responses. What evolutionary purpose could this have served?

Quintana-Murci: Reducing immune inflammatory responses is a way to avoid autoimmunity, inflammatory and allergic reactions. Finding that reduced immune responses has conferred an advantage highlights the tradeoff between recognizing pathogens while avoiding exacerbated, aberrant reactions that can be also harmful for the host.

RG: What are the next steps in this research?

Quintana-Murci: A fraction of the population differences in transcriptional responses to the immune stimulation observed is not explained by genetics, suggesting that other mechanisms, such as epigenetic variation, may explain such population differences. Knowing that epigenetic regulation is highly dynamic, the next step will be to explore whether and how epigenetic changes (methylation, histone modifications, DNA hypersensitivity sites, for example) occur during infection, and how these changes impact the expression of immune-related genes, including those showing differential expression across populations. In addition, in this work we focused on an intermediate molecular phenotype, i.e. gene expression. The next step is now to understand how gene expression differences are translated into differences in protein abundance. Furthermore, there is still much work to be done on how sex and aging also affect the regulation of gene expression in the context of immune responses and, more generally, in our different susceptibilities to infection, both at the individual and population levels.

Image courtesy of Benjamin Lehman.