Toll-Like Receptors Trigger Immune Response

Toll-like receptors (TLRs) are found in or on immune system cells and direct the immune system to fight disease. Compounds targeting one specific TLR, known as Toll-like receptor 9 (TLR9), have been developed for the treatment of cancer, infectious diseases, and allergy.

The human immune system has 10 TLRs, which enable immune cells to sense threats from both intracellular pathogens (such as viruses and retroviruses) and extracellular pathogens (including most bacteria and fungi) that cause human disease. To fight off intracellular pathogens, which act by spreading disease inside a cell in the body, TRLs help the immune system to mount a response that is called the Th1 response.

TLR9 is found in certain human immune cells and functions to detect a pattern that is present in the DNA of invading intracellular pathogens. When TLR9 detects this pattern, which is called a CpG motif, it triggers a Th1 response. Coley's Therapeutics (Wellesley, MA, USA) has focused its efforts on TLR9. Researchers there have developed TLR9 agonists (stimulators) that are synthetic oligonucleotides, comprising short, DNA-like sequences, which mimic CpG motifs found in some intracellular pathogens and trigger the body's immune response.

Coley's TRL agonists initiate a cascade of cellular signals to direct a highly specific and targeted immune response. They initiate both an innate and adaptive immune response, generating cytotoxic T cells and disease-specific antibodies against both tumors and pathogens. In addition, TLR9 agonists fight against the development of immune tolerance to pathogens and cancer.



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