Complement Evasion in Borrelia spirochetes: Mechanisms and Opportunities for Intervention

Abstract

Lyme disease (LD) is an increasingly prevalent, climate change-accelerated, vector-borne infectious disease with significant morbidity and cost in a proportion of patients who experience ongoing symptoms after antibiotic treatment, a condition known as post-treatment Lyme disease syndrome (PTLDS). Spirochetal bacteria of Borrelia species are the causative agents of LD. These obligate parasites have evolved sophisticated immune evasion mechanisms, including the ability to defeat the innate immune system’s complement cascade. Research on complement function and Borrelia evasion mechanisms, focusing on human disease, is reviewed, highlighting opportunities to build on existing knowledge. Implications for the development of new antibiotic therapies having the potential to prevent or cure PTLDS are discussed. It is noted that a therapy enabling the complement system to effectively counter Borrelia might have lower cost and fewer side-effects and risks than broad-spectrum antibiotic use and could avert the need to develop and administer a vaccine.

Lyme Disease Frontiers: Reconciling Borrelia Biology and Clinical Conundrums

“…Immune evasion strategies used by Borrelia to establish infection have been extensively reviewed elsewhere [35,[156][157][158][159][160][161][162][163]. Thus, the detailed biochemistry of host subversion is beyond the scope of this communication.…”

“…Subsequent work identified that OspC protects Borrelia from macrophage phagocytosis [134], although it is not yet known whether it functions as part of the IL-10 defense. Borrelia also has the capacity to resist the burst of reactive oxygen species produced by advancing phagocytes, via manganese superoxide dismutase antioxidation [163].…”

Hematological Features in Sheep with IgG and IgM Antibodies against Borrelia burgdorferi sensu lato

“…The presence of both IgM and IgG antibodies was assessed, in order to identify recent or previous exposure to Borrelia species. Although antibody kinetics is unknown in sheep as in other animals, studies in humans revealed the presence of IgM antibodies at about 3 days after infection [44]. A weak antibody reaction was evidenced in a patient from the first day of infection in another study, which became stronger within a week [45].…”

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

“…The first line of defense implemented by the immune system to protect the host against pathogens is known as the complement system. The complement system is a tightly regulated cascade of enzymatic proteins responsible for the opsonization of pathogens, phagocytosis, cell lysis, and the establishment of the membrane attack complex (MAC) [ 6 , 7 ]. There are three main activation pathways: the classical pathway (CP), the alternative pathway (AP), and the lectin pathway (LP) ( Figure 1 ).…”