Immune responses to infectious microbes vary among individuals within a population, and between different populations—a result of selective pressures from environmental and genetic factors, as well as from the infectious microbes themselves. Now, results from a new study show—for the first time—marked differences in the immune response to infectious microbes between Americans of African descent and Americans of European descent. These differences are mostly genetic—inherited from our ancestors and influenced by relatively recent natural selection.
The study (Genetic Ancestry and Natural Selection Drive Population Differences in Immune Responses to Pathogens), published in the journal Cell on October 20, 2016, was carried out in a human population consisting of 175 American individuals, 80 of African descent, and 95 of European descent. The 175 participants provided blood samples. The researchers used the blood samples to obtain macrophages—a type of white blood cell that wears many hats during the immune response. One of the macrophages’ functions is to participate in the innate immune response by sensing the presence of infectious microbes, and keeping these microbes under control while initiating the inflammatory response. During the inflammatory response, macrophages directly kill the invading microbes through a process called phagocytosis. In addition, they release chemical messengers that call other white blood cells to help resolve the infection, while moving the immune response to the next stage—the adaptive immunity stage.
The researchers infected the macrophages with live bacteria, either Listeria monocytogenes (a Gram-positive bacterium) or Salmonella typhimurium (a Gram-negative bacterium). These intracellular bacterial species specifically infect macrophages and, if the immune response is not strong enough, are able to grow and multiply within them. The researchers found markedly stronger response to infection induced in macrophages from individuals of African descent. Indeed, African ancestry specifically predicted a stronger inflammatory response and reduced intracellular bacterial growth. This effect was particularly noticeable when macrophages were infected with Listeria. There were no significant difference in the initial number of bacteria infecting macrophages. However, 24 hours after infection, the number of bacteria inside the macrophages from individuals with high levels of African ancestry was 3.2-fold lower than that of macrophages from individuals of European ancestry. The study results also show that these differences are under genetic control.
Luis Barreiro, senior author of the study, said in a press release: “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.”
Indeed, while short-term inflammation is necessary to eliminate invading microbes, long-term inflammation may lead to the development of chronic inflammatory disorders, as for example cardiovascular disease, or certain autoimmune diseases.
Barreiro added: “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.”