Pattern recognition receptors in health and diseases

Abstract

Pattern recognition receptors (PRRs) are a class of receptors that can directly recognize the specific molecular structures on the surface of pathogens, apoptotic host cells, and damaged senescent cells. PRRs bridge nonspecific immunity and specific immunity. Through the recognition and binding of ligands, PRRs can produce nonspecific anti-infection, antitumor, and other immunoprotective effects. Most PRRs in the innate immune system of vertebrates can be classified into the following five types based on protein domain homology: Toll-like receptors (TLRs), nucleotide oligomerization domain (NOD)-like receptors (NLRs), retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), C-type lectin receptors (CLRs), and absent in melanoma-2 (AIM2)-like receptors (ALRs). PRRs are basically composed of ligand recognition domains, intermediate domains, and effector domains. PRRs recognize and bind their respective ligands and recruit adaptor molecules with the same structure through their effector domains, initiating downstream signaling pathways to exert effects. In recent years, the increased researches on the recognition and binding of PRRs and their ligands have greatly promoted the understanding of different PRRs signaling pathways and provided ideas for the treatment of immune-related diseases and even tumors. This review describes in detail the history, the structural characteristics, ligand recognition mechanism, the signaling pathway, the related disease, new drugs in clinical trials and clinical therapy of different types of PRRs, and discusses the significance of the research on pattern recognition mechanism for the treatment of PRR-related diseases.

Current Understanding of the Innate Control of Toll-like Receptors in Response to SARS-CoV-2 Infection

“…Innate immune responses are the first line of defense against pathogens entering the body and are responsible for the priming of adaptive immune responses. Innate immune cells express pattern-recognition receptors, such as TLRs, retinoic acid-inducible gene-I-like receptors, nucleotide-binding oligomerization domain-like receptors, C-type lectin receptors, and absent in melanoma-2-like receptors, to recognize pathogen-associated molecular patterns (PAMPs) on pathogens [36]. Among them, TLRs play a crucial role in the activation of innate immune responses against various pathogens (Table 1).…”

Function and Molecular Mechanism of the DNA Damage Response in Immunity and Cancer Immunotherapy

“…Activation of the innate immune response relies on Pattern Recognition Receptors (PRRs). These PRRs detect Damage-Associated Molecular Patterns (DAMPs) or Pathogen-Associated Molecular Patterns (PAMPs) to initiate a signaling cascade resulting in production of interferons (IFNs), cytokines and chemokines ( 24 , 26 , 31 ). Importantly, non-self nucleic acids are the most well-characterized stimuli for the innate immune response ( 32 , 33 ); furthermore, endogenous cytosolic DNA released from the nucleus or mitochondria stimulates the innate immune system.…”

The Role of Epithelial Damage in the Pulmonary Immune Response

“…Like epithelial cells, innate immune cells express a broad range of PRRs and are consequently able to sense and respond to epithelial-derived stressors to shape the immune response. Persistent stimulation of PRRs on immune cells by epithelial-derived DAMPs can result in dysregulation of normal wound healing responses, causing a hyper inflammatory microenvironment, tissue destruction and dysregulation of normal wound healing [114]. Multiple immune cell types are reported to have altered signalling in pulmonary disease, effectively skewing the immune response to perpetuate inflammation and fibrosis.…”