The Immune Modulating Effects of the Borrelia Genus

If you were to ask the International Lyme and Associated Diseases Society (ILADS) the definition of Chronic Lyme Disease, they would tell you “Lyme disease is a bacterial infection caused by members of the Borrelia burgdorferi sensu lato complex” (Controversies and Challenges, n.d.). ILADS believes that Lyme Disease is ONLY a bacterial infection that is “often multisystemic – involving joints, heart, and the nervous system” (Controversies and Challenges, n.d.). From ILADS perspective, Lyme Disease is a bacterial infection that can lead to chronic inflammation and autoimmunity. However, when it comes to understanding the spirochetes, it is quite the opposite. Which leaves one very important unanswered question: Why is the main driver of the disease not discussed by ILADS?

Due to its ability to undergo antigenic variation (see other blogs), Spirochetes are able to shed their Outer Surface Proteins (Osps) to avoid being detected by the immune system (Brunner, Dunn, Luft & Schutzer, 1994). Similarly, to a gecko that can drop its tail to evade predators; the Lyme spirochetes shed blebs (OspA) when the immune system attempts to attack the spirochetes. 

These blebs assist the Lyme bacteria in evading the immune system by preventing it from mounting a response to the presenting antigens. Once these blebs are shed, the immune system releases a ‘cytokine storm’ which forces the immune system to shut itself off to avoid septic shock.

The small dots in the picture below are the blebs shed by Borreliae spirochetes

Typically, after a cytokine storm (sepsis like episode), the host often falls into a “a subsequent immunosuppressive phase” (Aosasa, 2018, p. 351). More specifically, those who are exposed to OspA often end up with a non-HIV mediated form of immunosuppression (Baumgarth, Elsner, Hastey & Olsen, 2015). It has been documented that those whose immune system failed to elicit a strong B-cell response, were most likely to have severe and lasting symptoms after treatment (Research Supported, 2018).  In the end, those exposed to OspA (Tick bite/LYMErix) often end up with B-cell immune disorders (immature B-cells/low antibodies).

Rather than ILADS notion that Chronic Lyme is ONLY a disease that causes inflammation and autoimmunity, they need to address the fact that it is  a disease of immunosuppression caused by the shedding of OspA.

In order to accurately define the mechanism behind ‘chronic Lyme Disease, ILADS must address the fact that OspA can lead to tolerance and cross-tolerance in the immune system of the host (Abbott, Boom, Harding, Li, Liu & Simmons, 2012). Endotoxin tolerance is one of the key mechanisms that reduces the “cytokine storm’ during sepsis” (Xiong et al, 2015, p. 171). However, endotoxin tolerance also “compromises the ability to counteract infections in septic shock survivors” (Xiong et al, 2015, p. 171). This is the reason that treatment fails iin so many cases. In one study, researchers determined that  “Six months after treatment, 15 of the 29 patients in the study had fully recovered, while 13 had persistent symptoms, and one had dropped out.”Lyme Disease, 2016, p. 2). Understanding that chronic Lyme Disease is a disease of tolerance and cross tolerance is the missing key to understanding why treatment fails in half the cases.

Simply put, tolerance (in the immune system) means that the immune system is no longer able to recognize pathogens that are managed by the Toll-like Receptors (TLR) that have become tolerant.
As mentioned in my other blogs, OspA affects TLR 2/1.

In addition, OspA can also lead to what is called cross-tolerance; whereby the immune system is unable to recognize infections managed by TLR 7/9 (Abbott, Boom, Harding, Li, Liu & Simmons, 2012). Since the immune system becomes tolerant to certain pathogens, Chronic Lyme Disease should be recognized as a form of non-HIV induced immunosuppression. Once exposed to OspA, the lymphocytes become tolerant TLR 2/1 and 7/9 (i.e. Candida, EBV, CMV, coxsackievirus, and other herpesviruses).

This is why so many people infected with Lyme Disease are seronegative. Because OspA, like other  triacylated lipoproteins (i.e. M. Tuberculosis), are known to downregulate the antigen-presenting molecules (HLAs or MHC class II) which leads to a “reduction of antigen presentation” (Boom & Harding, 2010, p.296). Why can triacylated lipoproteins lead to immunosuppression in diseases like M. Tuberculosis and not diseases like Lyme that involve OspA? In addition, tricylated lipoproteins like OspA also inhibit apoptosis (a natural process whereby cells “commit suicide” to avoid progression of disease). 

As a result, a large amount of Lyme sufferers end up with immature B-cells that are unable to efficiently eradicate opportunistic infections and keep latent viruses at bay leading to immunosuppression and chronic inflammation in the brain.

 When you understand these mechanisms, it is easy to understand why the CDC/IDSA/ALDF are able to confidently defend against chronic infection being the driving force behind “Chronic Lyme Disease”.  Because their own research shows that the driving force behind Chronic Lyme Disease is in the damage caused by the triacylated lipoprotein, OspA.

This leads to immunoparalysis/tolerance and cross tolerance to opportunistic infections and reactivated viruses (Xiong et al, 2015, p. 171). As you can see, the CDC/IDSA/ALDF deny Chronic Lyme (AKA. persistent bacteria) as being the main driver in disease because they know that tolerance and cross-tolerance are why many remain ill after long term antibiotic treatment.

In summary, tolerance may be described as the inability of the immune systems toll-like receptors to detect or fight off pathogens that are assigned to these specific receptors.  Whereas, cross tolerance occurs when Osps affect the toll-like receptors that are specifically assigned to fight off reactivated viruses like EBV, etc. Once this occurs, autoimmunity can become a problem for those who are infected with reactivated viruses and opportunistic infection.

When ILADS says that Lyme is a disease of autoimmunity, they fail to mention that this happens secondary to immunosuppression caused by OspA. For those who experience the MS and Lupus outcomes of Lyme, there is an autoimmune or HLA-linked response to the secondary opportunistic like HHV-6, CMV, and EBV (Wucherpfennig, (2001). 

When it comes to ‘Chronic Lyme’ it is important to understand that “there are other infectious organisms — Epstein-Barr virus, for example — that can produce similar symptoms and may be the real culprits.”  (Brody, 2013, p. 2). Thus, leaving the immunosuppressive effects of Lyme Disease out of case definitions is leading to the suffering of millions of people all around the world.

When you understand how OspA works, it’s easy to understand why antibiotics cannot alone cure “chronic Lyme Disease”.  Also, these mechanisms can help us understand why antibiotics usually only help to temporarily relieve many Lyme Disease sufferers of their symptoms. Antibiotics can help some people feel relief as it helps treat secondary infections that have taken over due to the tolerance and cross tolerance that occurs on account of being exposed to lipoproteins like OspA. This is also the key factor in why so many people relapse following antibiotic treatment. In the end, it is imperative that ILADS conducts more research on the immunosuppressive effects of OspA so that they can help develop a case definition that encompasses all outcome of Lyme Disease.


Abbott, D., Boom, W., Harding , C., Li , X., Liu, Y., & Simmons, D. (2012). TLR2 Signaling Depletes IRAK1 and Inhibits Induction of Type I IFN by TLR7/9. The Journal of Immunology, 188(3), 1019–1026. doi: 10.4049/jimmunol.1102181

Aosasa, S., Hiraki , S., Ono , S., & Tsujimoto, H. (2018). Mechanisms of sepsis-induced immunosuppression and immunological modification therapies for sepsis. Annals of Gastroenterological Surgery, 2(5), 351–358. doi: 10.1002/ags3.12194

Baumgarth, N. A., Elsner , R. J., Hastey, C. J., & Olsen, K. (2015). Suppression of Long-Lived Humoral Immunity Following Borrelia burgdorferi Infection. PLOS Pathogens, 11(7). doi: 10.1371/journal.ppat.1004976

Boom, W., & Harding, C. (2010). Regulation of antigen presentation by Mycobacterium tuberculosis: a role for Toll-like receptors. Nature Reviews Microbiology, 8(4), 296–307. doi: 10.1038/nrmicro2321

Brody, J. E. (2013, July 8). When Lyme Disease Lasts and Lasts. Retrieved October 22, 2019, from

Brunner, M. E., Coyle, S. K., Dunn, J. J., Luft, B. J., & Schutzer, P. (1994). Early and specific antibody response to OspA in Lyme Disease. Journal of Clinical Investigation, 94(1), 454–457. doi: 10.1172/jci117346

Controversies and Challenges. (n.d.). Retrieved October 22, 2019, from

Lyme Disease May Be Diagnosable via Transcriptome Signature.” Genetic Engineering and Biotechnology News (GEN) , 12 Feb. 2016,

Research Supported by Bay Area Lyme Foundation Shows Lower Immune Response Leads To Persistent Lyme Disease Symptoms. (2018, August 23). Retrieved October 22, 2019, from

Wucherpfennig, K. W. (2001). Mechanisms for the induction of autoimmunity by infectious agents. Journal of Clinical Investigation, 108(8), 1097–1104. doi: 10.1172/jci14235

Xiong, Y., Murphy, M., Manavalan, T. T., Pattabiraman, G., Qiu, F., Chang, H.-H., … Medvedev, A. E. (2015). Endotoxin Tolerance Inhibits Lyn and c-Src Phosphorylation and Association with Toll-Like Receptor 4 but Increases Expression and Activity of Protein Phosphatases. Journal of Innate Immunity, 8(2), 171–184. doi: 10.1159/000440838

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