Peer-Reviewed Publications

Scientific Evidence - Peer-Reviewed Publications on Soluble Toll-like Receptor 2 (sTLR2)

This section provides peer-reviewed publications that underscore sTLR2's significance in innate immunity, sepsis pathogenesis, inflammation, and its potential in diagnostic and prognostic applications.

Summary

Human Toll-like receptor 2 (sTLR2), a receptor of the immune system critically involved in pro-inflammatory responses, is present in plasma and other bodily fluids, and showed anti-inflammatory potential, acting as a decoy receptor to limit inflammation (1-5).

Notably, elevated levels of sTLR2 are present early on in patients with sepsis, and other infective and non-infective inflammatory conditions (1-18), having rapid kinetics of release.

Elevated sTLR2 levels can be detected in plasma after just 30 minutes following cell stimulation by bacterial products, reaching peak concentration after just 4 hours, and has a very short half-life. This represents an advantage as an early biomarker over CRP and procalcitonin (PCT), another biomarker of infection. CRP exhibits a slower kinetics of release, as it only begins to rise after 12-24 hours of the insult, peaking within 2-3 days, and PCT becomes elevated after 3-4 hours and peaks about 6-24 hours.

References

1. Soluble forms of Toll-like receptor (TLR)2 capable of modulating TLR2 signaling are present in human plasma and breast milk. LeBouder E. et al. J Immunol. 2003. 171: 6680-6689, and editorial commentary 171: 6321 https://doi.org/10.4049/jimmunol.171.12.6680

2. Soluble TLR2 reduces inflammation without compromising bacterial clearance by disrupting TLR2 triggering. Raby AC. et al. J Immunol. 2009. 183: 506-517.
https://doi.org/10.4049/jimmunol.0802909

3. Toll-Like Receptors 2 and 4 Are Potential Therapeutic Targets in Peritoneal
Dialysis–Associated Fibrosis. Raby AC. et al. J Am Soc Nephrol 2017 Feb;28(2):461-478.
http://dx.doi.org/10.1681/ASN.2015080923

4. Targeting Toll-Like Receptors with Soluble Toll-Like Receptor 2 Prevents Peritoneal Dialysis Solution-Induced Fibrosis. Raby AC. et al. Kidney International, 2018. 94:346-362.http://dx.doi.org/10.1016/j.kint.2018.03.014

5. Therapeutic targeting of chronic kidney disease-associated DAMPs differentially contributing to vascular pathology. Mazzarino M. et al. Front Immunol. 2023 Oct 2;14:1240679. https://doi.org/10.3389%2Ffimmu.2023.1240679

6. Soluble Toll-like receptor 2 is a biomarker for sepsis in critically ill patients with multi-organ failure within 12h of ICU admission. Holst B. et al. Intensive Care Med Exp. 2017 Dec;5(1):2

7. Amniotic fluid soluble Toll-like receptor 2 in pregnancies complicated by preterm prelabor rupture of membranes. Andrys C. et al. J Matern Fetal Neonatal Med. 2013; 26:520–7.

8. The Soluble Form of Toll-Like Receptor 2 Is Elevated in Serum of Multiple Sclerosis Patients: A Novel Potential Disease Biomarker. Hossain MJ et al. Front Immunol. 2018 Mar 14; 9: 457, 2018.

9. Milk matters: soluble Toll-like receptor 2 (sTLR2) in breast milk significantly inhibits HIV-1 infection and inflammation. Henrick BM et al. PLoS One. 2012; 7(7):e40138.

10. Soluble toll-like receptor 2 is significantly elevated in HIV-1 infected breast milk and inhibits HIV-1 induced cellular activation, inflammation and infection. Henrick BM et al. AIDS. 2014;28:2023-32

11. Soluble toll-like receptor 2 in HIV infection: association with disease progression. Heggelund L. et al. AIDS. 2004; 18: 2437-2439.

12. Serum soluble toll-like receptor 2: a novel biomarker for systemic lupus erythematosus disease activity and lupus-related cardiovascular dysfunction. Houssen ME et al. Int J Rheum Dis. 2016 Jul; 19:685-92. doi: 10.1111/1756-185X.12452. Epub 2014 Aug 14.

13. Characterization of soluble TLR2 and CD14 levels during acute dengue virus infection. Upasani V. et al. Heliyon 9 (2023) e17265

14. Soluble toll-like receptor 2 (TLR-2) is increased in saliva of children with dental caries. Zhao A. et al. BMC Oral Health. 2014; 14:108

15. Membrane and soluble Toll-like receptor 2 in patients with psoriasis treated by Goeckerman therapy. Kondelkova K. et al. Int J Dermatol. 2014; 53(11):e512-7. doi: 10.1111/ijd.12381.

16. Toll-Like Receptor 2 in Serum: a Potential Diagnostic Marker of Prosthetic Joint Infection? Galliera E. et al. J. Clin. Microbiol. 2014; 52: 620-623.

17. The Role of Soluble TLR-2 in the Immunopathogenesis of Gingivitis. BH Al-Ghurabi - International Medical Journal, 2021; Vol. 28, Supplement No. 1, pp. 37 – 39

18. Insights into Soluble Toll-Like Receptor 2 as a Downregulator of Virally Induced Inflammation. Henrick BM et al. Front. Immunol. 2016. 7:291. doi: 10.3389/fimmu.2016.00291

19. Association between soluble Toll-like receptor 2 concentrations and confirmed diagnosis of sepsis: results of a case-control study. Y. Lim, T. Szakmany, A.-C. Raby, M.O. Labéta. Br. J. Anaesth. 2018. Vol: 121, Issue: 2, Page: e26-e27. DOI10.1016/j.bja.2018.05.033