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.

Gene Co-expression Networks Identifies Common Hub Genes Between Cutaneous Sarcoidosis and Discoid Lupus Erythematosus

“…Toll-like receptors recognize pathogen-associated molecular pathways (PAMPS) that are expressed on infectious agents ( 38 ). TLR1 in particular is expressed at higher levels than other TLRs and has been associated with infectious diseases that affect the skin, including Leprosy ( 39 ) and Lyme Disease ( 40 ). TLRs are thought to play a role in both sarcoidosis and lupus pathogenesis ( 41 , 42 ), and has been suggested as a potential therapeutic target for lupus ( 43 ).…”

The Potential of Omics Technologies in Lyme Disease Biomarker Discovery and Early Detection

“…A number of single-nucleotide polymorphisms (SNPs) in the TLR genes [13] and their downstream factors [60, 61] were recently proposed to modulate the host response to infection. These SNPs alter the TLR signaling patterns and may have an impact on the clinical manifestations of bacterial, fungal and viral infections [62].…”

“…Inflammation, induced by either the spirochete or its antigens in the affected tissues, is thought to play a major role in LB pathogenesis at both the early and late disease stages [ 12 , 13 ]. Early inflammatory responses distinguish patients from healthy controls and diverge from those of other diseases with overlapping clinical features [ 12 ].…”

“…Early inflammatory responses distinguish patients from healthy controls and diverge from those of other diseases with overlapping clinical features [ 12 ]. The final outcome of infection, however, is dependent on the intricate interaction between the pathogen and the host immune response [ 12 , 13 ]. Therefore, elucidating the extent of alteration in the host inflammatory and immunological pathways at the early stages of host-pathogen interaction may provide an insight into the potential mechanisms rendering B. burgdorferi -infected subjects susceptible to disseminated LB and, perhaps, the later development of post-treatment Lyme disease syndrome (PTLDS).…”

“…Therefore, elucidating the extent of alteration in the host inflammatory and immunological pathways at the early stages of host-pathogen interaction may provide an insight into the potential mechanisms rendering B. burgdorferi -infected subjects susceptible to disseminated LB and, perhaps, the later development of post-treatment Lyme disease syndrome (PTLDS). It may also facilitate characterizing an array of biomarkers for various disease stages that can serve as targets for new diagnostic techniques and assist in development of therapies [ 13 ].…”