MONTREAL, Oct. 20, 2016 - A Canada-US study led by Luis Barreiro, a professor at the University of Montreal's Department of Pediatrics and researcher at the Sainte-Justine University Hospital Center, has demonstrated that Americans of African descent have a stronger immune response to infection compared to Americans of European descent. The study establishes for the first time this difference in immune responses and shows that it is mostly genetic -- inherited from our ancestors and influenced by a relatively recent natural selection. The study is published today in the scientific journal Cell.
The study was conducted among 175 Americans, half of which were of African descent, the other half being of European descent, in collaboration with the University of California, Wayne State University, Cornell University, the University of Minnesota, and Duke University.
While the immune system of African Americans responds more strongly, Professor Barreiro is careful to qualify it as better: "The immune system of African Americans responds differently, but we cannot conclude that it is better, since a stronger immune response also has negative effects, including greater susceptibility to autoimmune inflammatory diseases such as Crohn's disease. Too much inflammation can damage organs and leave sequelae. In short, a strong immune response can be beneficial in some areas but a disadvantage in others.
Susceptibility to inflammatory diseases
The immune system reacts to infection by causing inflammation (redness, heat, swelling, etc.) to neutralize and eliminate the infection. It was already known to scientists that African Americans are more susceptible to autoimmune inflammatory diseases and thus more likely to suffer from tuberculosis or scleroderma, for example.
The laboratory experiment
The 175 participants in Professor Barreiro's study provided blood samples, from which were extracted macrophages ¬-- cells of the immune system whose role is to kill pathogens responsible for infection. The research team then infected the macrophages with two kinds of bacteria (Listeria and Salmonella) to observe various immune responses: after 24 hours of infection, the macrophages from African Americans killed the bacteria three times faster. The research team also uncovered the molecular mechanisms acting on the genes responsible for these differences in immune responses. "This is one of the firsts of our study," said Barreiro. People of African and European descent have intermingled over the past centuries, and we are even able to determine which part of an individual's immune system is associated with African ancestry and which part with European ancestry."
Why these differences?
"Although we found these differences in immune responses between African and European Americans, we are still unable to demonstrate what evolutionary pressures led to the observed differences. One of our hypotheses is that in the prehistoric period, after human populations had migrated out of Africa, they were exposed to fewer pathogens (bacteria, viruses, parasites), which reduced the immune response and thus tissue inflammation. This reduction in the immune response (and inflammation) was most likely an advantage because of the adverse consequences of acute or chronic inflammation, which are major contributors to the development of autoimmune inflammatory diseases."
Another hypothesis is that the weaker immune response detected in Europeans is the result of a less vigorous natural selection in an environment in which there were fewer, or at least different, pathogens compared to Africa.
The role of Neanderthals
Neanderthals also played a role in the immune response to infection. Neanderthals, before disappearing, colonized Europe, but not Africa. In the process, they mixed their genes with African Cro-Magnons, who were spread throughout Europe. The analysis of Barreiro's team shows that about 3% of the genes involved in the differences in immune responses between African and European Americans come from Neanderthals!
"There is still much to do. For example, we have not yet studied the immune response to viruses and parasites. In addition, genetics explains only about 30% of the observed differences in immune responses. Our future studies should focus on other factors, emphasizing the influence of the environment and our behaviour. The idea is to find immune mechanisms to help understand why some individuals react differently from others in the presence of certain viruses and bacteria," said Barreiro.
About Luis Barreiro
Luis Barreiro specializes in the evolution of immune responses and was named one of the "40 under 40" (most promising researchers) published in 2014 by the prestigious journal Cell. The first time he set foot in a laboratory after completing his graduate studies in biotechnology at the University of Lisbon in his native Portugal, he found his vocation. After graduating, he obtained a six-month internship in mycobacterial genetics at the Pasteur Institute in Paris. Within five years he had completed a doctorate in human population genetics. After receiving his Ph.D., Barreiro moved to the United States, where he did a postdoctoral fellowship in functional genomics at the University of Chicago's Department of Human Genetics.
Today, the same theme runs through Luis Barreiro's work at the University of Montreal and the Sainte-Justine University Hospital Research Center, which he joined in 2011. He is the holder of the Canadian Research Chair in Functional and Evolutionary Genomics of the Immune System. The main project of his laboratory is to discover and define the genetic bases of the variations underlying the differences in immune responses between individuals and human populations. While Barreiro's team is among the two or three groups in the world interested in immune responses and their genetic basis, it is the only one to explore this issue among different species of primates.
About the study
Y. Nedelec, J. Sanz, G. Baharian, Z. A. Szpiech, A. Pacis, A. Dumaine, J.-C. Grenier, A. Freiman, A. J. Sams, S. Hebert, A. Pagé Sabourin, F. Luca, R. Blekhman, R. D. Hernandez, R. Pique-Regi, J. Tung, V. Yotova et L. B. Barreiro published the article "Genetic ancestry and natural selection drive population differences in immune responses to pathogens in human" in the journal Cell on October 2016.
Funding for the study
This study was funded by the Canadian Institutes of Health Research (Grants 301538 and 232519), the Human Frontiers Science Program (CDA-00025/2012), and the Canada Research Chairs Program (950-228993). Y.N. received a grant from the Network of Applied Genetic Medicine Network (RMGA); A.P.S. received a grant from the Fonds de recherche du Québec-Nature et technologies (FRQNT); and G.B. received a grant from the Fonds de recherche du Québec-Santé (FRQS).