pattern recognition receptor signaling pathway

Definition

Target type: biologicalprocess

The series of molecular signals initiated by a ligand binding to a pattern recognition receptor (PRR), and ending with the regulation of a downstream cellular process, e.g. transcription. PRRs bind pathogen-associated molecular pattern (PAMPs), structures conserved among microbial species, or damage-associated molecular pattern (DAMPs), endogenous molecules released from damaged cells. [GOC:add, GOC:ar, ISBN:0781735149, PMID:15199967]

Pattern recognition receptors (PRRs) are crucial components of the innate immune system, playing a vital role in recognizing and responding to a wide range of pathogens, including bacteria, viruses, fungi, and parasites. These receptors are expressed on various immune cells, such as macrophages, dendritic cells, neutrophils, and natural killer (NK) cells.

PRRs recognize conserved molecular patterns, known as pathogen-associated molecular patterns (PAMPs), that are specific to microbial invaders. These PAMPs include:

- Lipopolysaccharide (LPS) from bacterial cell walls
- Flagellin from bacterial flagella
- Peptidoglycans from bacterial cell walls
- CpG DNA motifs from bacterial and viral DNA
- Double-stranded RNA (dsRNA) from viruses
- Viral glycoproteins

Upon PAMP recognition, PRRs trigger a complex signaling cascade that activates downstream signaling pathways, leading to the production of inflammatory cytokines, chemokines, and other effector molecules. These responses aim to eliminate the invading pathogens, recruit immune cells to the site of infection, and initiate adaptive immune responses.

**Major PRR Families**

- **Toll-like receptors (TLRs):** TLRs are type I transmembrane proteins that recognize a diverse array of PAMPs. They are expressed on the cell surface and in intracellular compartments, enabling them to detect both extracellular and intracellular pathogens. TLR signaling pathways involve the activation of adaptor proteins such as MyD88 and TRIF, which lead to the activation of transcription factors like NF-κB and IRF3. These transcription factors induce the expression of inflammatory cytokines, type I interferons (IFNs), and other immune mediators.
- **RIG-I-like receptors (RLRs):** RLRs are cytoplasmic sensors of viral RNA. They recognize dsRNA and other viral RNA structures. Upon activation, RLRs activate downstream signaling pathways that involve MAVS (mitochondrial antiviral signaling protein) and ultimately lead to the production of type I IFNs.
- **NOD-like receptors (NLRs):** NLRs are cytosolic proteins that sense intracellular pathogens and cellular stress. They form inflammasomes, multiprotein complexes that activate caspase-1, a protease that cleaves pro-inflammatory cytokines such as IL-1β and IL-18. These cytokines promote inflammation and contribute to the clearance of pathogens.
- **C-type lectin receptors (CLRs):** CLRs are transmembrane proteins that recognize carbohydrate structures on pathogens. They are expressed on various immune cells and play a role in pathogen recognition, phagocytosis, and the activation of downstream signaling pathways.

**Key Features of PRR Signaling**

- **Specificity:** PRRs are highly specific for PAMPs, allowing them to discriminate between self and non-self.
- **Amplification:** PRR signaling involves a cascade of molecular events that amplify the initial signal, ensuring a robust response.
- **Integration:** Multiple PRRs can be activated simultaneously by different PAMPs, allowing for a coordinated immune response.
- **Crosstalk:** PRR signaling pathways often interact with other signaling pathways, including those involved in adaptive immunity.
- **Immune regulation:** PRR signaling not only activates immune responses but also regulates their duration and intensity, preventing excessive inflammation and tissue damage.

**Clinical Significance**

PRR signaling plays a critical role in host defense against infections. Dysregulation of PRR signaling can contribute to autoimmune diseases, inflammatory disorders, and susceptibility to infections. Understanding the molecular mechanisms of PRR signaling is essential for developing novel therapies for these conditions.

**Conclusion**

PRR signaling is a fundamental process in innate immunity. By recognizing conserved microbial patterns, PRRs initiate a cascade of signaling events that activate the immune system, leading to the elimination of pathogens and the establishment of protective immunity.'
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Proteins (6)

Compounds (70)