Effector Responses Induced by Pattern Recognition Receptors (PRRs) for Disease Protection

Background. Pattern Recognition Receptors (PRRs) represent fundamental components of the innate immune system responsible for detecting pathogenassociated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Understanding PRR-mediated effector responses is essential for developing therapeutic strategies and enhancing disease protection mechanisms.
Objective. To comprehensively review the mechanisms of PRR activation, classification, and their pivotal role in orchestrating effector responses for disease protection, while examining their therapeutic implications and potential clinical applications.
Methods. This review analyzes current literature on PRR biology, focusing on their classification into membrane-bound (Toll-like receptors, C-type lectin receptors), cytoplasmic (NOD-like receptors, RIG-I-like receptors), and soluble (collectins, pentraxins) types. The study examines intracellular signaling pathways, including MyD88-dependent and TRIF-dependent pathways, and their downstream effects on immune cell activation.
Results. PRRs demonstrate remarkable versatility in detecting diverse microbial threats and initiating tailored immune responses. Upon activation, PRRs trigger complex signaling cascades involving NF-κB and interferon regulatory factors (IRFs), leading to cytokine production, inflammation, and immune cell recruitment. Different infection types (bacterial, viral, fungal, parasitic) elicit specific PRR-mediated responses: bacterial infections activate complement and promote phagocytosis; viral infections induce interferon production and cytotoxic T lymphocyte responses; fungal infections stimulate Th1-mediated immunity; and parasitic infections trigger eosinophil activation and Th2 responses. PRRs also play crucial regulatory roles, preventing hyperinflammation and promoting immune tolerance.
Conclusions. PRRs function as master regulators of immune responses, serving not only as pathogen detectors but also as sophisticated coordinators of immune activation, tolerance, and resolution. While dysregulated PRR signaling contributes to autoimmunity and chronic inflammatory diseases, targeted modulation of PRR pathways offers promising therapeutic opportunities. Future research directions include exploring novel PRR subtypes, developing precision immunomodulatory therapies, and addressing challenges in translating PRR-based interventions from bench to bedside.
Clinical Significance. Understanding PRR-mediated effector responses provides insights into disease pathogenesis, offers potential drug targets for infectious and inflammatory diseases, and supports the development of individualized treatment approaches for enhanced immune protection.

1. Land W.G. Damage-associated molecular patterns in human diseases, SpringerLink. Available at: https://link.springer.com/book/10.1007/978-3-319-78655-1

2. Suresh R., Mosser D.M. Pattern recognition receptors in innate immunity, host defense, and immunopathology. Advances in physiology education. 2013. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4089092/

3. Zaru R. Bitesized Immunology: Receptors & Molecules, BSI Immunology. Available at: https://www.immunology.org/publicinformation/bitesized-immunology/receptorsmolecules/pattern-recognition-receptor-prrs

4. Wicherska-Pawłowska K., Wróbel T. and Rybka J. Toll-like receptors (tlrs), NOD-like receptors (nlrs), and rig-i-like receptors (rlrs) in innate immunity. tlrs, nlrs, and rlrs ligands as immunotherapeutic agents for hematopoietic diseases, International journal of molecular sciences. 2021. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704656/#:~:text = Several%20classes%20of%20PRRS%2C%20including,and%20RLRs%20are%20intracellular%20molecules

5. Li D., Wu M. Pattern recognition receptors in health and diseases, Signal transduction and targeted therapy. 2021. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8333067/

6. Hu W., Pasare C. Location, location, location: Tissue-specific regulation of immune responses, Journal of leukocyte biology. 2013. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3747123/

7. Jannuzzi G.P. et al. Intracellular prrs activation in targeting the immune response against fungal infections, Frontiers. 2020. Available at: https://www.frontiersin.org/articles/10.3389/fcimb.2020.591970/full

8. Dagenais A., Villalba-Guerrero C., Olivier M. Trained immunity: A ‘new’ weapon in the fight against infectious diseases, Frontiers. 2023. Available at: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1147476/full

9. Funes S.C. et al. Trained immunity contribution to autoimmune and inflammatory disorders, Frontiers. 2022. Available at: https://www.frontiersin.org/articles/10.3389/fimmu.2022.868343/full

10. 10 Land W.G. Damage-associated molecular patterns in human diseases volume 3: Antigenrelated disorders. Cham: Springer International Publishing. 2023.