Genes and Age Determine Susceptibility to Lyme Disease

Despite the importance of immune variation for the symptoms and outcome of Lyme disease, the factors influencing cytokine production during infection with the causal pathogen Borrelia burgdorferi remain poorly understood.

People react very differently to an infection with the Borrelia bacterium that causes Lyme disease, however, despite the large differences observed; the bacterium has a clear effect on the immune system’s energy regulation, opening up opportunities for studies into better detection of Borrelia infections.

An international team of scientists led by those at Radboud University Medical Center (Nijmegen, the Netherlands) investigated how differences in cytokine production during a Borrelia infection in 500 healthy volunteers can be explained. Borrelia infection-induced monocyte- and T cell-derived cytokines were profiled in peripheral blood from two healthy human cohorts of Western Europeans from the Human Functional Genomics Project. Both non-genetic and genetic host factors were found to influence Borrelia-induced cytokine responses.

The team found that the immune response to Lyme disease appears to be strongly age-related. Production of the cytokine interleukin-22 (IL-22) deceases with age, reducing the immune system's defense against the Borrelia bacteria. They also found a genetic variation that increases production of the hypoxia-inducible factor 1-alpha (HIF-1a) protein during a Borrelia infection. This protein causes the amount of lactic acid in the cell to increase, which normally only happens at low oxygen levels. This results in an energy deficiency in the immune cells and therefore a reduction in the production of IL-22 and other inflammatory proteins.

One million people are bitten by a tick in the Netherlands each year, and about one in five of these ticks are carriers of the Borrelia bacterium. The symptoms after an infection vary widely: for example, many people have a red ring or patch around the bite, but some do not. This can make it difficult to give a correct diagnosis. Leo A B Joosten, PhD, a professor of Pathobiology and senior author of the study, said, “We had expected that people with Borrelia antibodies in their blood would have a stronger immune response to the Borrelia bacteria. However, that is not the case. It seems that the Borrelia bacterium does not cause improved resistance.” The study was published on November 3, 2016, in the journal Cell Host & Microbe.

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Radboud University Medical Center