The Brilliance of Borrelia: Mechanisms of Host Immune Evasion by Lyme Disease-Causing Spirochetes

Abstract

Lyme disease (LD) has become the most common vector-borne illness in the northern hemisphere. The causative agent, Borrelia burgdorferi sensu lato, is capable of establishing a persistent infection within the host. This is despite the activation of both the innate and adaptive immune responses. B. burgdorferi utilizes several immune evasion tactics ranging from the regulation of surface proteins, tick saliva, antimicrobial peptide resistance, and the disabling of the germinal center. This review aims to cover the various methods by which B. burgdorferi evades detection and destruction by the host immune response, examining both the innate and adaptive responses. By understanding the methods employed by B. burgdorferi to evade the host immune response, we gain a deeper knowledge of B. burgdorferi pathogenesis and Lyme disease, and gain insight into how to create novel, effective treatments.

Keywords: Borrelia; Lyme disease; adaptive; complement; immune response; innate.

Figure 1

Formation of the membrane attack complex formation via the alternative, classical, and lectin pathways. The alternative pathway is activated by the binding of C3b directly to the surface of a microbe. The classical pathway activation is triggered by the presence of antigen–antibody complexes. The lectin pathway is activated by the binding of mannose-binding lectins to mannose-containing liposaccharides on the surface of the pathogen. Created with BioRender.com; https://biorender.com/ (accessed on 1 March 2021).

Figure 2

Locations of interference for all three complement activation pathways. Red boxes were used to indicate sites of both direct and indirect inhibition involved in B. burgdorferi infection. Orange boxes indicate sites of compliment inhibition due to tick salivary proteins. Abbreviations: Osp, outer surface protein; TSLPI, tick salivary lectin pathway inhibitor; Salp, salivary protein; Isac/Irac/Ixac, Ixodes anti-complement proteins. Created with BioRender.com.

Figure 3

Illustration of antigenic variation, a tactic used by pathogens to avoid detection by the hosts immune system. Evasion is accomplished by the continuous change in a prominent surface antigen through gene conversion events or change in allelic expression. Created with BioRender.com.