Prophylactic and therapeutic implications of toll-like receptor ligands

Mona Hedayat, Kiyoshi Takeda, Nima Rezaei
Medicinal Research Reviews 2012, 32 (2): 294-325
The evolutionary conserved Toll-like receptors (TLRs) are the first identified and best characterized pattern recognition receptors (PRRs) which discriminate self from nonself, providing an early and effective immune response against invading pathogens. The ever expanding knowledge of TLR signaling network make it one of the most promising therapeutic strategies to modulate the immune response in various human diseases. Immune modulating strategies based on TLR-specific agonists elicit a potent immune response to adjuvant vaccine immunotherapy, cancers, allergic diseases, and chronic viral infections while minimizing the risk of uncontrolled provocation of systemic inflammatory response. Moreover, the contribution of TLR signaling in the pathogenesis of chronic noninfectious inflammatory and autoimmune diseases provides the rationale for the development and clinical implementation of TLR-specific antagonists. At present, a few TLR-specific agonists have been approved for both prophylactic and therapeutic applications, while the ongoing preclinical and clinical studies show promising results on various novel therapeutic molecules as an adjunctive to conventional pharmacotherapy or stand-alone therapeutic strategy.

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