New Study From Netherlands Sheds Light on Chronic Lyme

New Study From Netherlands Sheds Light on Chronic Lyme

People’s immune system react very differently to Lyme disease based on recent research published by Radboud University Medical Center, the University Medical Center Groningen (UMCG), the Broad Institute of MIT and Harvard recently (Oct 2016) in Cell Host & Microbe.

Age, genetic disposition and previous Lyme infections play an important role, but despite the large differences observed, the Borrelia bacterium has a clear effect on the immune system’s energy regulation. The highlights from the study:

  • Borrelia-induced cytokine production in human PBMCs resembles intracellular bacteria
  • Borrelia-induced IL-22 and IFN-γ, but not IL-17, responses decrease with age
  • HIF-1α-regulation of glucose metabolism is crucial for cytokine induction by Borrelia
  • HIF-1α expression and lactate production is enhanced in PBMCs from Lyme disease patients.

The variation in immune response can be largely explained by differences in the production of cytokines, the most important signalling molecules in our immune system. The Human Functional Genomics Project, run by professors Mihai Netea and Leo Joosten at Radboud University Medical Center, UMCG Professor Cisca Wijmenga and Professor Ramnik Xavier at the Broad Institute of MIT and Harvard investigated how differences in cytokine production during a Borrelia infection in 500 healthy volunteers can be explained.

“Inflammation is the body’s attempt at self-protection. Its goal is to remove harmful stimuli, including damaged cells, irritants, or pathogens so that the body can begin the healing process. Lyme and its coinfections incite a hyper-response of cytokine formation,” explains DO Tracie Leonhardt in Lyme and Lyme-Like Disease: The New Epidemic published in the July 2016 issue of Townsend Letter.

“Cytokines are proteins made of various types of white blood cells with their function being to make antibodies work more effectively, increase WBC activity, recruit other WBCs to the site of infection, and decrease viral and bacterial replication. Cytokines are produced when infection, oxidizing agents, cytokines, toxins, and other agents stimulate immune cells. Once the immune cells are stimulated, NF-KB causes genetic programming for the production of cytokines and the activation of the leukocytes. With Lyme and other related infections, there is an overproduction of cytokines, inducing an excessive inflammatory response that leads to chronic inflammation. This may manifest itself as a suppressed immune system, pain, reduced hormonal production from the thyroid and adrenal glands, sleep disturbances, cognitive decline, fatigue, myalgias, and depression.

“The dysregulation of cytokines and chemokines is a central feature in the development of neuroinflammation, neurodegeneration, and demyelination in both the central and peripheral nervous systems. This process can lead to activation of the microglia, which may mediate neuronal and glial cell injury and death through the production of the pro-inflammatory factors such as cytokines.”

The Netherlands recent study included Forest rangers, who receive as many as 35 tick bites per day. “Some of them had never had Lyme disease, even though the chance of infection was high.” reported researcher Joosten.

First of all, the immune response to Lyme disease appears to be strongly age-related. Production of the cytokine IL-22 deceases with age, reducing the immune system’s defense against the Borrelia bacteria. The researchers also found a genetic variation that increases production of the 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.

This effect on the metabolism of immune cells is specific to the Borrelia bacterium, which opens up possibilities for research into the better detection and treatment of a Borrelia infection.

According to Joosten, “It is not possible to measure IL-22 in patient’s blood so we have no new test. We do however want to look at whether blocking the lactic acid route could help, but that is difficult to do at cell level. Another way is to strengthen the immune system by raising the levels of IL-22 but we would rather find ways to increase the immune system’s ability to kill the Borrelia bacteria.”

It is interesting that previous Borrelia infections do not seem to provide protection from Lyme disease Joosten says. “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. We hope that further research will show how previous Lyme infections specifically affect the immune system.”

Over the past decades, Lyme disease has confounded researchers and treatment specialists alike in the bacteria’s ability to trick the immune response by either over-stimulating or under-stimulating the immune response. This results in antibody levels that are inconsistent with active infections, and also causes false negatives in spite of symptoms.

Ultimately it is hoped that this research will open up new opportunities for research into better detection of Borrelia infections, and ultimately effective treatment.


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