Toll-like Receptors
Overview
Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single, membrane-spanning, non-catalytic receptors usually expressed in sentinel cells such as macrophages and dendritic cells, that recognize structurally conserved molecules derived from microbes. Once these microbes have breached physical barriers such as the skin or intestinal tract mucosa, they are recognized by TLRs, which activate immune cell responses.
Structure
TLRs are a type of pattern recognition receptor (PRR) and recognize molecules that are broadly shared by pathogens but distinguishable from host molecules, collectively referred to as pathogen-associated molecular patterns (PAMPs). TLRs together with the Interleukin-1 receptors (IL-1Rs) form a receptor superfamily, known as the "interleukin-1 receptor / toll-like receptor superfamily", all members of which have in their cytoplasmic domain a conserved stretch of approximately 200 amino acids known as the TIR domain.
Function
TLRs are involved in both innate and adaptive immunity. In the innate immune response, TLRs recognize PAMPs and activate signaling pathways such as the NF-κB pathway, which lead to an inflammatory response. In the adaptive immune response, TLRs stimulate antigen-presenting cells (APCs), which affects T cell responses. TLRs may also play a role in apoptosis and other cellular processes.
Types
There are at least 13 types of TLRs in mammals, each of which recognizes a specific class of PAMPs. TLRs are named numerically (e.g., TLR1, TLR2, etc.). TLRs are present in vertebrates, as well as invertebrates, and plants, and even in bacteria.
Role in Disease
TLRs have a key role in the detection and control of infections. However, their role in various diseases is complex. On the one hand, TLRs can initiate an immune response against pathogens, which can help to clear the infection. On the other hand, excessive or chronic activation of TLRs can lead to pathological inflammation, which can contribute to a variety of diseases, including sepsis, autoimmune diseases, and cancer.
Research and Therapeutic Applications
Research into TLRs has potential applications in the treatment of various diseases. For example, TLR agonists are being investigated as potential vaccines or vaccine adjuvants. TLR antagonists are being investigated for the treatment of inflammatory and autoimmune diseases.