At Eurofins Discovery, our Biomarker Services offer innovative assays aimed at developing treatments for autoimmune diseases such as lupus, arthritis, psoriasis, COVID-19, and cancer.
Toll-like receptors (TLRs) play a vital role in the regulation of innate immunity and are identified as the earliest determinant of immune activation. From an immunological perspective, TLR agonists or their inhibitors may play a pivotal role as therapeutic agents to manage these diseases, and more.
TLRs represent an important group of pattern-recognition receptors (PRRs) of the host defense system, which recognize a specific molecular pattern in microbes, pathogens, and host cell-damaged molecules. TLRs are present on immune cells including dendritic cells, macrophages, monocytes, neutrophils, T cells, B cells, mast cells, natural killer cells, and in the non-immune cells including epithelial cells, astrocytes, fibroblasts, keratinocytes, and platelets.
Key Components of Toll-like Receptor Signalling
Figure. The Toll-like receptor (TLR) and myeloid differentiation primary response 88 (MyD88) pathway is a signaling cascade activated by the recognition of pathogen-associated molecular patterns (PAMPs) by TLRs. This pathway is essential for the activation of the innate immune response and the subsequent initiation of the adaptive immune response. When a pathogen invades the body, PAMPs on its surface are recognized by TLRs, which are transmembrane receptors expressed on various immune and non-immune cells. Each TLR recognizes a specific set of PAMPs, such as lipopolysaccharides (LPS) from Gram-negative bacteria, flagellin from bacteria, or viral RNA. Upon binding of a PAMP to the TLR, the TLR undergoes a conformational change and dimerizes with another TLR molecule, leading to the recruitment of the adapter protein MyD88 to the cytoplasmic domain of the TLR. MyD88 then recruits and activates a series of downstream signaling molecules, including IRAK (IL-1 receptor-associated kinase) and TRAF6 (TNF receptor-associated factor 6). IRAK and TRAF6 activate several signaling cascades, including the NF-κB and MAPK pathways, which lead to the activation of transcription factors, such as NF-κB and AP-1, and the subsequent transcription of genes encoding proinflammatory cytokines and chemokines, such as TNF-α, IL-1β, IL-6, and CXCL8. These cytokines and chemokines recruit and activate immune cells, such as neutrophils, macrophages, and dendritic cells, to the site of infection, and stimulate the differentiation of T cells.
TLRs are linked to infectious diseases including bacterial, viral, and fungal – including COVID-19. Pathogens stimulate TLRs, which induce the synthesis of cytokines and chemokines to clear the infection. Recent evidence indicates a role for TLR4 in SARS–CoV-2 infection, through enhancing ACE-2 expression on the cell surface which in turn facilitates virus entry.
The established role of TLRs in autoimmune disease includes: systemic lupus erythematosus, rheumatoid arthritis, psoriasis, and some cancers. From an immunological perspective, TLR agonists or their inhibitors may play a pivotal role as therapeutic agents to manage these diseases.
Our Biomarker Services experts are working in this promising therapeutic area, providing TLR stimulation and inhibition functional assays to screen compounds using human peripheral blood mononuclear cells (PBMCs) with validated cytokine/chemokines as readouts using multiplex technology. We also customize TLR assays according to your specific needs.
- Plasma Membrane TLR Assays
TLR 1/2, TLR 2/6, TLR 4 and TLR5 for those wanting cell surface biomarker assessments - Intracellular TLR Assays
TLR 7/8 and TLR9 assays are specific for these intracellular subtypes - Consider Custom Options
Additional readouts in combination with TLR biomarkers, as well as in species other than human, are possible
