Toll-like receptor cascade and gene polymorphism in host–pathogen interaction in Lyme disease

Abstract

Lyme disease (LD) risk occurs in North America and Europe where the tick vectors of the causal agent Borrelia burgdorferi sensu lato are found. It is associated with local and systemic manifestations, and has persistent posttreatment health complications in some individuals. The innate immune system likely plays a critical role in both host defense against B. burgdorferi and disease severity. Recognition of B. burgdorferi, activation of the innate immune system, production of proinflammatory cytokines, and modulation of the host adaptive responses are all initiated by Toll-like receptors (TLRs). A number of Borrelia outer-surface proteins (eg, OspA and OspB) are recognized by TLRs. Specifically, TLR1 and TLR2 were identified as the receptors most relevant to LD. Several functional single-nucleotide polymorphisms have been identified in TLR genes, and are associated with varying cytokines types and synthesis levels, altered pathogen recognition, and disruption of the downstream signaling cascade. These single-nucleotide polymorphism-related functional alterations are postulated to be linked to disease development and posttreatment persistent illness. Elucidating the role of TLRs in LD may facilitate a better understanding of disease pathogenesis and can provide an insight into novel therapeutic targets during active disease or postinfection and posttreatment stages.

Keywords:

• Lyme disease
• Toll-like receptors
• Borrelia lipoproteins
• genetic polymorphisms
• host-pathogen interaction

Acknowledgments

The authors thank Dr Paul Arora for discussing the manuscript. This work was supported by a fund from the Public Health Agency of Canada.

Author contributions

AB conceived the study idea and design. AB, SR, and MS prepared the first draft of the manuscript. NHO and RL helped in drafting the article and contributed to study design. All authors critically reviewed the manuscript, approved the final draft, and agreed to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.