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Pattern Recognition Receptors

Pattern Recognition Receptors Background

About Pattern Recognition Receptors

Pattern recognition receptors (PRRs) are essential components of the innate immune system, playing a vital role in its proper functioning. PRRs serve as innate sensors encoded in the germline, allowing them to detect specific molecules associated with pathogens. These receptors are primarily expressed by cells of the innate immune system, such as dendritic cells, macrophages, monocytes, neutrophils, and epithelial cells. They recognize two main classes of molecules: pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs).

PRRs are often referred to as primitive pattern recognition receptors because they evolved before other components of the immune system, including adaptive immunity. They not only detect PAMPs and DAMPs but also play a crucial role in initiating the adaptive immune response specific to the encountered pathogen. Additionally, PRR activation leads to the release of inflammatory cytokines, contributing to the immune response.

PAMPs are specific molecules found in microbes that are recognized by PRRs. They encompass a range of components, including bacterial carbohydrates (such as lipopolysaccharide or LPS, mannose), nucleic acids (bacterial or viral DNA or RNA), bacterial peptides (e.g., flagellin, microtubule elongation factors), peptidoglycans, lipoteichoic acids (found in Gram-positive bacteria), N-formylmethionine, lipoproteins, fungal glucans, and chitin.

DAMPs, on the other hand, are endogenous stress signals associated with components released from damaged or dying host cells. Examples of DAMPs include uric acid, extracellular ATP, and various other compounds.

Toll-like receptor 4 - Creative BioMart

Types of Pattern Recognition Receptors

Based on their localization, PRRs may be divided into membrane-bound PRRs and cytoplasmic PRRs:

  • Membrane-bound PRRs include toll-like receptors (TLRs) and C-type lectin receptors (CLRs).
  • Cytoplasmic PRRs include NOD-like receptors (NLRs) and RIG-I-like receptors (RLRs).

PRRs were first discovered in plants. Since that time many plant PRRs have been predicted by genomic analysis (370 in rice; 47 in Arabidopsis). Unlike animal PRRs, which are associated with intracellular kinases via adaptor proteins (see non-RD kinases below), plant PRRs are composed of an extracellular domain, transmembrane domain, juxtamembrane domain, and intracellular kinase domain as part of a single protein.

Ligand Recognition and Downstream Signaling

PRRs recognize conserved molecular patterns present in pathogens, such as bacterial cell wall components, viral nucleic acids, and fungal cell wall carbohydrates. These patterns are distinct from host molecules and are recognized as non-self by the immune system. PRRs have evolved to recognize a wide range of PAMPs, allowing the immune system to detect a diverse array of pathogens.

Upon ligand recognition, PRRs initiate intracellular signaling cascades that lead to the activation of immune responses. This involves the recruitment of adaptor proteins, activation of signaling pathways (such as NF-κB and MAPK pathways), and subsequent production of pro-inflammatory cytokines, chemokines, type I interferons, and antimicrobial molecules. These immune mediators help eliminate the pathogen and shape the overall immune response.

Innate Immune Responses and Priming of Adaptive Immunity

PRR activation triggers innate immune responses, which are the immediate defense mechanisms against pathogens. These responses include inflammation, recruitment of immune cells to the site of infection, activation of phagocytosis, and induction of antimicrobial activities.

Additionally, PRR activation plays a crucial role in priming adaptive immune responses by promoting antigen presentation and co-stimulatory molecule expression on antigen-presenting cells.

Dysregulation and Disease

When pattern recognition receptors (PRRs) become dysfunctional or dysregulated, it can have significant implications for disease development and progression. Here are some key points regarding the association between PRR dysfunction and disease:

  • Autoimmune Diseases: Dysregulation of PRR signaling can contribute to the development of autoimmune diseases. Inappropriate activation or impaired regulation of PRRs may lead to the recognition of self-molecules as foreign, triggering an immune response against the body's tissues. This can result in chronic inflammation and tissue damage seen in conditions such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis.
  • Chronic Inflammatory Disorders: Dysregulated PRR signaling can also contribute to chronic inflammatory disorders. Excessive or prolonged activation of PRRs can lead to persistent inflammation, tissue damage, and organ dysfunction. Conditions like inflammatory bowel disease, asthma, and chronic obstructive pulmonary disease (COPD) have been associated with dysregulated PRR responses.
  • Infectious Diseases: Dysfunction of PRRs can impact the host's ability to recognize and respond to microbial pathogens effectively. Defects in PRR signaling pathways may result in reduced immune responses, impaired clearance of pathogens, and increased susceptibility to infections. For example, mutations in specific PRR genes have been linked to increased susceptibility to certain viral, bacterial, and fungal infections.
  • Cancer: Dysregulation of PRRs has been implicated in cancer development and progression. Aberrant PRR signaling can contribute to chronic inflammation, which creates an environment favorable for tumor growth and metastasis. Additionally, altered PRR expression or function in tumor cells or immune cells within the tumor microenvironment can impact immune surveillance, immune evasion, and anti-tumor immune responses.
  • Metabolic Disorders: Emerging evidence suggests a connection between dysfunctional PRR signaling and metabolic disorders, including obesity and insulin resistance. Chronic low-grade inflammation driven by dysregulated PRRs can disrupt insulin signaling pathways and promote insulin resistance, contributing to the development of type 2 diabetes and metabolic syndrome.

Understanding the relationship between PRR dysfunction and disease is crucial for developing targeted therapies and interventions. Modulating PRR signaling pathways and restoring their proper function may offer potential strategies for treating immune-related disorders, reducing chronic inflammation, and improving disease outcomes.

Available Resources for Pattern Recognition Receptors

To support PRR research, we offer a wide range of recombinant proteins that are crucial for studying their structure, function, and interactions. Our recombinant proteins are produced using advanced expression and purification techniques to ensure high purity and quality. We offer a diverse selection of PRR proteins, including Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I-like receptors (RLRs), C-type lectin receptors (CLRs), and more.

In addition to our extensive catalog of recombinant proteins, we provide personalized services tailored to the specific needs of our clients. Our experienced scientists are available to assist with custom protein production, protein modification, protein labeling, and protein-protein interaction studies, among other services. We strive to deliver high-quality results promptly, ensuring that researchers have the tools they need to advance their PRR research.

To further support PRR research, we also offer comprehensive resources to assist researchers in their studies. Our online database provides detailed information on PRR-related pathways, protein functions, interacting proteins, and relevant articles. This wealth of information helps researchers gain a deeper understanding of PRR biology and facilitates the discovery of new therapeutic targets and treatment strategies.

Our Advantages

Our advantages - Creative BioMart

At Creative BioMart, we are committed to advancing PRR research by providing high-quality tools, personalized services, and comprehensive resources. We understand the importance of this field and aim to contribute to the discovery of new insights and therapies in PRR-related diseases. Contact us today to learn more about our offerings and how we can support your PRR research.

References:

  1. Jang JH, Shin HW, Lee JM, Lee HW, Kim EC, Park SH. An Overview of Pathogen Recognition Receptors for Innate Immunity in Dental Pulp. Mediators Inflamm. 2015;2015:794143. doi:10.1155/2015/794143
  2. Li D, Wu M. Pattern recognition receptors in health and diseases. Signal Transduct Target Ther. 2021;6(1):291. Published 2021 Aug 4. doi:10.1038/s41392-021-00687-0
  3. Amarante-Mendes GP, Adjemian S, Branco LM, Zanetti LC, Weinlich R, Bortoluci KR. Pattern Recognition Receptors and the Host Cell Death Molecular Machinery. Front Immunol. 2018;9:2379. Published 2018 Oct 16. doi:10.3389/fimmu.2018.02379
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