Targeting pattern-recognition receptors to discover new small molecule immune modulators.

Abstract

Pattern recognition receptors (PRRs) are key immune receptors of the innate immune system, which recognize the conserved pathogen-associated molecular patterns (PAMPs) of the invading pathogens. Compared to the adaptive immune receptors, PRRs have three distinguishing features, viz., universal expression, fast response and recognizing many kinds of microbes. Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), C-type lectin receptors (CLRs) and NOD-like receptors (NLRs) recognize viral nucleic acid/bacterial fragments and trigger anti-microbial innate immune responses. Upon recognition of their ligand species, PRRs recruit specific intracellular adaptor proteins to initiate signaling pathways culminating in the activation of nuclear factor-κB (NF-κB), mitogen-activated protein (MAP) kinases and interferon regulatory factors (IRFs) that control the transcription of genes encoding pro-inflammatory factors including type I interferon and other inflammatory cytokines, which are critical for eliminating the potential threat to the host. Here, we summarize the effects of small molecule regulators acting on signaling pathways initiated by TLR, RLR and NLR as well as their influence on innate and adaptive immune responses leading to therapy.

• Authors: Gengzheng Zhu, Yao Xu, Xiaohong Cen, Kutty Selva Nandakumar, Shuwen Liu, Kui Cheng
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 144 Pg. 82-92 (Jan 20 2018) ISSN: 1768-3254 [Electronic] France
• PMID: 29268133 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Chemical References

• Immunologic Factors
• Receptors, Pattern Recognition
• Small Molecule Libraries

Topics

• Adaptive Immunity (drug effects)
• Animals
• Drug Discovery
• Humans
• Immunity, Innate (drug effects)
• Immunologic Factors (chemistry, pharmacology)
• Inflammation (drug therapy, immunology)
• Molecular Targeted Therapy
• Receptors, Pattern Recognition (immunology)
• Small Molecule Libraries (chemistry, pharmacology)