cell surface pattern recognition receptor signaling pathway

Definition

Target type: biologicalprocess

The series of molecular signals initiated by a ligand binding to a cell surface pattern recognition receptor (PRR). PRRs bind pathogen-associated molecular pattern (PAMPs), structures conserved among microbial species. [GOC:add, GOC:ar, ISBN:0781735149, PMID:15199967]

Cell surface pattern recognition receptors (PRRs) are crucial components of the innate immune system, acting as the first line of defense against invading pathogens. These receptors are strategically positioned on the cell surface and within intracellular compartments, constantly surveying the environment for danger signals.

PRRs recognize highly conserved molecular patterns, known as pathogen-associated molecular patterns (PAMPs), that are characteristic of microbial pathogens. These PAMPs include molecules like lipopolysaccharide (LPS) from bacteria, flagellin from bacterial flagella, and viral double-stranded RNA.

Upon encountering a PAMP, PRRs initiate a signaling cascade that triggers a variety of immune responses aimed at eliminating the threat. This signaling pathway involves a complex interplay of adaptor proteins, kinases, and transcription factors.

**The key steps in cell surface PRR signaling pathway are:**

1. **PAMP Recognition:** The PRR binds to its specific PAMP, initiating the signaling cascade.

2. **Adaptor Protein Recruitment:** Binding of the PAMP triggers the recruitment of adaptor proteins, such as MyD88 or TRIF, to the PRR complex.

3. **Activation of Kinases:** The adaptor proteins activate downstream kinases, including IRAKs and TRAF6.

4. **Signal Amplification:** Activated kinases initiate a signaling cascade that amplifies the initial signal.

5. **Activation of Transcription Factors:** The signaling cascade culminates in the activation of transcription factors, such as NF-κB and IRF3.

6. **Gene Expression and Immune Responses:** Activated transcription factors translocate to the nucleus, where they induce the expression of a wide array of genes involved in immune responses, including:
* **Cytokine Production:** Proinflammatory cytokines like TNF-α, IL-1β, and IL-6 are produced to recruit immune cells to the site of infection.
* **Antimicrobial Peptide Production:** Antimicrobial peptides are released to directly kill invading pathogens.
* **Type I Interferon Production:** Type I interferons are secreted to inhibit viral replication.
* **Co-stimulatory Molecule Expression:** Expression of co-stimulatory molecules on antigen-presenting cells is enhanced to activate adaptive immune responses.

7. **Immune Cell Activation:** The signaling pathway ultimately leads to the activation and recruitment of immune cells, such as macrophages, neutrophils, and NK cells, to combat the invading pathogen.

**The diverse array of PRRs and their associated signaling pathways allows for the detection and response to a wide range of pathogens.**

**Examples of cell surface PRRs:**

* **Toll-like receptors (TLRs):** TLRs are a family of PRRs that recognize a diverse range of PAMPs, including LPS, flagellin, and viral nucleic acids.
* **C-type lectin receptors (CLRs):** CLRs recognize carbohydrates and other glycans found on pathogens.
* **Retinoic acid-inducible gene-I-like receptors (RLRs):** RLRs detect viral double-stranded RNA.

The cell surface PRR signaling pathway plays a critical role in the early stages of immune defense, initiating a rapid and effective response to invading pathogens.'
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