The mammalian immune system is equipped with pattern-recognition receptors as a mechanism to recognize conserved structural motifs, including both pathogen- and danger-associated molecular patterns. The purpose is to generate protective immune responses towards pathogens or damaged cells. An important family of receptors are known as Toll-like receptors (TLRs). The TLRs are type 1 transmembrane proteins, comprising an extracellular domain of leucine-rich repeats and cysteine-rich motifs as well as an intracellular domain of Toll/IL-1 receptor homology (TIR), in which the TIR domain is essential for the signalling. To date there have been 10 human TLRs characterized, which can be categorized into two subclasses: cell-surface TLRS (TLR1, TLR2, TLR4, TLR5, TLR6) and endosomal TLRs (TLR3, TLR7, TLR8 and TLR9). Those TLRs therefore enable human cells to recognize divergent types of molecules expressed by microbial cells or by damaged mammalian cells, such as bacterial lipopolysaccharide, single-stranded RNA or CpG DNA.
The TLRS are predominantly expressed by cells of innate immune systems, including epithelial cells, endothelial cells, macrophages and dendritic cells. Activation of TLRs would stimulate innate immune systems to release pro-inflammatory cytokines (e.g., TNF-alpha, IL-12 and IL-18) and type I interferons, which in return activate the adaptive arm of the immune system as well. Thus, TLR activation would trigger protective immune responses. We and other groups have shown that mucosal-associated T cells, mainly residing in the liver and lungs, were activated during TLR8 activation and as result conferred antibacterial and antiviral protection. Due to this immune response-generating property, TLR agonists could be used as an adjuvant in vaccine formulation. Yet an excessive TLR stimulation could backfire as it would disrupt immune homeostasis, causing many inflammatory or autoimmune diseases, such as asthma and systemic lupus erythematosus. Thus, modulating TLR signalling, through activation or inhibition, might have merits in preventing and treating diseases linked to immune dysregulation. Elucidation of the involved molecular mechanisms in rescuing the immune dysregulation would provide an impetus to translate these scientific discoveries into clinical practice.
This Research Topic proposes to gather data analysing the mechanisms, safety and efficacy of using TLR agonists or inhibitors as a means to prevent or treat diseases linked to immune dysregulation. We therefore welcome the submission of Original Research, Methods, Perspective, Review or Mini-Review pieces that cover, but are not limited to, the following topics.
Molecular mechanisms of TLR agonists or inhibitors:
- as antiviral or antibacterial agents
- to (re-)activate immune systems during chronic viral infection
- in their formulations as vaccine adjuvants
- in cancer treatment
- as treatment options in inflammatory and autoimmune diseases
Topic editor Johan Garssen is employed by Danone Nutricia Research. All other Topic Editors declare no competing interests with regards to the Research Topic subject.
The mammalian immune system is equipped with pattern-recognition receptors as a mechanism to recognize conserved structural motifs, including both pathogen- and danger-associated molecular patterns. The purpose is to generate protective immune responses towards pathogens or damaged cells. An important family of receptors are known as Toll-like receptors (TLRs). The TLRs are type 1 transmembrane proteins, comprising an extracellular domain of leucine-rich repeats and cysteine-rich motifs as well as an intracellular domain of Toll/IL-1 receptor homology (TIR), in which the TIR domain is essential for the signalling. To date there have been 10 human TLRs characterized, which can be categorized into two subclasses: cell-surface TLRS (TLR1, TLR2, TLR4, TLR5, TLR6) and endosomal TLRs (TLR3, TLR7, TLR8 and TLR9). Those TLRs therefore enable human cells to recognize divergent types of molecules expressed by microbial cells or by damaged mammalian cells, such as bacterial lipopolysaccharide, single-stranded RNA or CpG DNA.
The TLRS are predominantly expressed by cells of innate immune systems, including epithelial cells, endothelial cells, macrophages and dendritic cells. Activation of TLRs would stimulate innate immune systems to release pro-inflammatory cytokines (e.g., TNF-alpha, IL-12 and IL-18) and type I interferons, which in return activate the adaptive arm of the immune system as well. Thus, TLR activation would trigger protective immune responses. We and other groups have shown that mucosal-associated T cells, mainly residing in the liver and lungs, were activated during TLR8 activation and as result conferred antibacterial and antiviral protection. Due to this immune response-generating property, TLR agonists could be used as an adjuvant in vaccine formulation. Yet an excessive TLR stimulation could backfire as it would disrupt immune homeostasis, causing many inflammatory or autoimmune diseases, such as asthma and systemic lupus erythematosus. Thus, modulating TLR signalling, through activation or inhibition, might have merits in preventing and treating diseases linked to immune dysregulation. Elucidation of the involved molecular mechanisms in rescuing the immune dysregulation would provide an impetus to translate these scientific discoveries into clinical practice.
This Research Topic proposes to gather data analysing the mechanisms, safety and efficacy of using TLR agonists or inhibitors as a means to prevent or treat diseases linked to immune dysregulation. We therefore welcome the submission of Original Research, Methods, Perspective, Review or Mini-Review pieces that cover, but are not limited to, the following topics.
Molecular mechanisms of TLR agonists or inhibitors:
- as antiviral or antibacterial agents
- to (re-)activate immune systems during chronic viral infection
- in their formulations as vaccine adjuvants
- in cancer treatment
- as treatment options in inflammatory and autoimmune diseases
Topic editor Johan Garssen is employed by Danone Nutricia Research. All other Topic Editors declare no competing interests with regards to the Research Topic subject.
