Toll-like receptors: promising therapeutic targets for inflammatory diseases

Abstract

The health of living organisms is constantly challenged by bacterial and viral threats. The recognition of pathogenic microorganisms by diverse receptors triggers a variety of host defense mechanisms, leading to their eradication. Toll-like receptors (TLRs), which are type I transmembrane proteins, recognize specific signatures of the invading microbes and activate a cascade of downstream signals inducing the secretion of inflammatory cytokines, chemokines, and type I interferons. The TLR response not only counteracts the pathogens but also initiates and shapes the adaptive immune response. Under normal conditions, inflammation is downregulated after the removal of the pathogen and cellular debris. However, a dysfunctional TLR-mediated response maintains a chronic inflammatory state and leads to local and systemic deleterious effects in host cells and tissues. Such inappropriate TLR response has been attributed to the development and progression of multiple diseases such as cancer, autoimmune, and inflammatory diseases. In this review, we discuss the emerging role of TLRs in the pathogenesis of inflammatory diseases and how targeting of TLRs offers a promising therapeutic strategy for the prevention and treatment of various inflammatory diseases. Additionally, we highlight a number of TLR-targeting agents that are in the developmental stage or in clinical trials.

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

“…For example, various TLRs have now also been implicated in the pathogenesis of neurodegenerative disorders including Parkinson's disease (PD), Alzheimer's disease (AD), Amyotrophic lateral sclerosis (ALS) and repair mechanism is brain disorders [496][497][498][499][500]. Thus, TLRs are playing an important role in infectious and non-infectious disease and are targeted as therapeutic approaches in these diseases [501,502]. Even studies have shown that these TLRs are controlling mammalian reproduction via regulating the process of steroidogenesis, spermatogenesis in males and ovulation, fertilization, gestation, and parturition in females [503][504][505][506].…”

Syk Plays a Critical Role in the Expression and Activation of IRAK1 in LPS-Treated Macrophages

“…The inflammatory response is controlled by several immune cells, such as macrophages, dendritic cells, neutrophils, and eosinophils [1–3]. These cells express several receptors, including the toll-like receptors (TLR), which recognize exogenous pathogens or infected materials and then promote the activation of these receptors, thereby triggering a variety of cellular responses, including the expression and activation of inflammation regulatory genes such as cytokines, adhesion molecules, costimulatory molecules, and chemokines [4–7]. The transcription and translation of these genes rely on the activation of additional transcription factors as well as their upstream signaling cascades [8].…”

Guizhi-jia-houpu-xingzi decoction attenuates ovalbumin-induced allergic asthma via regulation of Toll-like receptor signal pathway

“…[23,24]. TLRs can recognize specific conserved molecular components of microorganisms and then transfer the signals into the cell, leading to the activation of NF-κB [25,26].…”