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Immunopathogenesis of Lyme disease

Linden Hu, MD
Section Editor
Allen C Steere, MD
Deputy Editor
Jennifer Mitty, MD, MPH


Advances in the understanding of the interactions that occur between Borrelia burgdorferi and its mammalian and tick hosts have led to important insights into the pathogenic mechanisms that underlie the manifestations of human Lyme disease. With the sequencing of the B. burgdorferi genome came several surprising insights. Among these is the fact that B. burgdorferi has a very small genome compared with other bacteria. It does not encode for any toxins or lipopolysaccharides, but does encode a large number of lipoproteins relative to other bacteria. Also missing from its genome are genes that enable bacteria to synthesize such essential products as amino acids, fatty acids, enzyme cofactors, and nucleotides. As such, B. burgdorferi is dependent upon its environment to provide these nutrients and has evolved specialized mechanisms for adapting to its different environments.

The lifecycle of B. burgdorferi requires that it survive in two distinct environments — that found in a tick host and that found in a mammalian host. The challenges posed by these environments differ greatly. Because ticks do not thermoregulate, while in the tick host B. burgdorferi must survive at the extremes of ambient temperatures found in winter and summer in its areas of geographic distribution. In addition, ticks take only one blood meal every 6 to 12 months, and as a result, B. burgdorferi must be able to survive with minimal nutrition for long periods of time.

In contrast, life in a mammalian host provides a stable temperature and an abundance of nutrients. However, compared with ticks, which have rudimentary immune systems, mammals have highly sophisticated immune defenses. The ability of B. burgdorferi to cause long-term infection in mammalian hosts requires that it implement strategies to successfully evade and subvert host immune defenses. Optimal host immune control of B. burgdorferi infection requires both innate and adaptive immune systems. However, neither system, alone or in combination, is able to completely eradicate the organism in mice despite resolution of signs of infection and inflammation. In humans, it appears that the immune system can eventually eradicate the infection, since almost all patients eventually resolve their symptoms even without antibiotics [1]. In Europe, B. afzelii has been cultured from skin lesions of patients in Europe with acrodermatitis atrophicans after greater than 10 years [2], but this genotype is not present in the United States.

In this topic, we will describe some of the mechanisms that B. burgdorferi uses to establish infection as well as the host immune responses to invasion by the organism that both help control the infection and also cause some of the manifestations of Lyme disease. The microbiology, epidemiology, clinical manifestations, diagnosis, prevention, and treatment of Lyme disease are discussed separately. (See "Epidemiology of Lyme disease" and "Clinical manifestations of Lyme disease in adults" and "Lyme disease: Clinical manifestations in children" and "Diagnosis of Lyme disease" and "Prevention of Lyme disease" and "Evaluation of a tick bite for possible Lyme disease" and "Treatment of Lyme disease".)


Bacterial adaptations

Outer surface protein variations — B. burgdorferi exit the tick while it feeds on a mammalian host and establish infection in the skin. To transit from the tick midgut, where the B. burgdorferi are located prior to initiation of feeding, to the tick salivary gland, the organism rapidly downregulates a protein called outer surface protein A (OspA) and upregulates another protein called outer surface protein C (OspC) [3,4]. Downregulation of OspA accomplishes two tasks:


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Literature review current through: Sep 2016. | This topic last updated: Dec 7, 2015.
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