Single nucleotide polymorphisms of Toll-like receptors and susceptibility to infectious diseases

Abstract

SummaryToll-like receptors (TLRs) are the best-studied family of pattern-recognition receptors (PRRs), whose task is to rapidly recognize evolutionarily conserved structures on the invading microorganisms. Through binding to these patterns, TLRs trigger a number of proinflammatory and anti-microbial responses, playing a key role in the first line of defence against the pathogens also promoting adaptive immunity responses. Growing amounts of data suggest that single nucleotide polymorphisms (SNPs) on the various human TLR proteins are associated with altered susceptibility to infection. This review summarizes the role of TLRs in innate immunity, their ligands and signalling and focuses on the TLR SNPs which have been linked to infectious disease susceptibility.

Immune Interactions with Pathogenic and Commensal Fungi: A Two-Way Street

“…TLR1 variants are associated with increased risk for candidemia (Plantinga et al, 2012). Also, polymorphisms in TLR1, TLR4 , and TLR6 have been linked to aspergillosis in allogeneic hematopoietic stem cell transplant patients (Skevaki et al, 2015). …”

TLR8 and TLR9 Polymorphisms and Pulmonary Tuberculosis

“…Upon activation, TLRs initiate the expression of host genes in specific signaling cascades to regulate innate and adaptive immunity (5). Up to now, thirteen TLR members (TLR1 -TLR13) have been recognized in humans; each of them identifies various PAMPs from different microbial pathogens of bacterial, viral, fungal and protozoan origin (6). Among different TLRs, TLR1, TLR2, TLR4, TLR5, TLR6 and TLR11 are located on the cell surface, however TLR3, TLR7, TLR8 and TLR9 are localized on subcellular membranes.…”

“…Among different TLRs, TLR1, TLR2, TLR4, TLR5, TLR6 and TLR11 are located on the cell surface, however TLR3, TLR7, TLR8 and TLR9 are localized on subcellular membranes. It seems that TLR1, TLR2, TLR4, TLR6, TLR8 and TLR9 are involved in the recognition of mycobacterium (6).…”

Cell Signaling Pathways That Regulate Antigen Presentation

“…Lastly, signaling via TLRs have been predominantly associated with infectious diseases (118-124); however, a variety of single-nucleotide polymorphisms in human TLRs have not only been associated with infectious and inflammatory (including autoimmune) diseases, but also with cancer (121, 123-126). As such, TLRs have been looked at as potential targets for immune-based therapy against infectious diseases (118, 119), as well as sepsis-associated pathology (118).…”