Evaluation of Advanced Immune Markers (TLR4 and sTREM-1) among three Strains of Escherichia coli
Abstract:
These Escherichia coli strains (Uropathogenic - UPEC, Enteroaggregative – EAEC and Enterotoxigenic ETEC) are major pathogens involved in urinary tract infections, diarrhea diseases and systemic infections. They become pathogenic through adhesion factors, toxin synthesis and tissue colonization, inducing strong innate immune reactions. Toll-like receptor 4 (TLR4) and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) are important immune mediators representing both host recognition of bacterial moieties and further amplification of inflammation. In the present study we aimed to assess serum concentrations of TLR4 as well as sTREM-1 in patients infected with three distinct E. coli serotypes in comparison to healthy controls. Patients and methods A total of 65-cases (confirmed cases due to E. coli) were included at Hilla Teaching Hospital, Babylon/Iraq, over the period from March to September 2025 in addition to 50 apparently healthy subjects as controls. Exclusion criteria were recent antibiotic or anti-inflammatory treatment, chronic systemic diseases, pregnancy and lactation. Peripheral venous blood samples were obtained, the serum TLR4 and sTREM-1 levels in both groups were determined by ELISA. Results Serum levels of TLR4 (mean ≈ 5.8 ng/mL) and sTREM-1 (mean ≈ 152 pg/mL) were significantly raised in infected patients as compared to the controls (p < 0.05). Within strains, UPEC-infected patients had the greatest while EAEC- and ETEC-infected patients had lower responses; these findings suggest strain-specific differences in host immune activation. There were no important differences in experimental factors by sex or residence. These findings demonstrate that TLR4 and sTREM-1 are strong markers of innate immunity activation in E. coli infection, which could be used as additional biomarkers to assess host inflammatory response, follow disease activity and potentially differentiate between strain dependent pathogenic profiles.
KeyWords:
TLR4, sTREM-1, Escherichia coli, EAEC, ETEC, UPEC
References:
- Al-Fahham, A.A. (2018) Development of New LSD Formula when Unequal Observations Numbers of Observations Are. Open Journal of Statistics, , 8, 258-263.https://doi.org/10.4236/ojs.2018.82016.
- Alvestegui, A., Olivares‑Morales, M., Muñoz, E., Smith, R., Nataro, J.P., & Farfán, M.J. (2019). TLR4 participates in the inflammatory response induced by the AAF/II fimbriae from enteroaggregative Escherichia coli on intestinal epithelial cells. Frontiers in Cellular and Infection Microbiology, 9, 143. https://doi.org/10.3389/fcimb.2019.00143
- Bauer, M. E., & Welch, R. A. (2016). Impact of pathogen-specific virulence factors on host innate immune responses: Insights from uropathogenic Escherichia coli. Microbiology Spectrum, 4(1), 1–17. https://doi.org/10.1128/microbiolspec.UTI-0010-2012
- Bautista-Carbajal, P., Chávez-Pérez, J. P., García-León, M. L., Cabrera-Sánchez, J. A., Baltazar-López, N., Zaldivar-Ramirez, F. R., & Wong-Chew, R. M. (2025). sTREM-1 as a biomarker for sepsis diagnosis and prognosis following abdominal surgery. Laboratory medicine, lmaf074. Advance online publication. https://doi.org/10.1093/labmed/lmaf074
- Charles, P. E., Noel, R., Massin, F., Guy, J., Bollaert, P. E., Quenot, J. P., & Gibot, S. (2016). Significance of soluble triggering receptor expressed on myeloid cells-1 elevation in patients admitted to the intensive care unit with sepsis. BMC infectious diseases, 16(1), 559. https://doi.org/10.1186/s12879-016-1893-4
- Frendéus, B., Wachtler, C., Hedlund, M., Fischer, H., Samuelsson, P., Svensson, M., & Svanborg, C. (2001). Escherichia coli P fimbriae utilize the Toll-like receptor 4 pathway for cell activation. Molecular microbiology, 40(1), 37–51. https://doi.org/10.1046/j.1365-2958.2001.02361.x
- Geurtsen, J., de Been, M., Weerdenburg, E., Zomer, A., McNally, A., & Poolman, J. (2022). Genomics and pathotypes of the many faces of Escherichia coli. FEMS microbiology reviews, 46(6), fuac031. https://doi.org/10.1093/femsre/fuac031
- Gibot, S., Massin, F., Cravoisy, A., Barraud, D., Nace, L., & Bollaert, P.‐E. (2016). Outcomes of sTREM-1–guided management of suspected sepsis: A prospective multicenter study. Intensive Care Medicine, 42(4), 494–504.
https://doi.org/10.1007/s00134-015-4157-1 - Heine, H., & Zamyatina, A. (2022). Therapeutic Targeting of TLR4 for Inflammation, Infection, and Cancer: A Perspective for Disaccharide Lipid A Mimetics. Pharmaceuticals (Basel, Switzerland), 16(1), 23. https://doi.org/10.3390/ph16010023
- Jiang, J., Wang, X., Cheng, T., Han, M., Wu, X., Wan, H., & DaojunYu (2020). Dynamic Monitoring of sTREM-1 and Other Biomarkers in Acute Cholangitis. Mediators of inflammation, 2020, 8203813. https://doi.org/10.1155/2020/8203813
- Leatham‑Jones, C., Smith, J., & Wu, L. (2022). The immune responses to different uropathogens call individual interventions for bladder infection. Frontiers in Immunology, 13, 953354. https://doi.org/10.3389/fimmu.2022.953354
- Olson, P. D., & Hunstad, D. A. (2016). Subversion of Host Innate Immunity by Uropathogenic Escherichia coli. Pathogens (Basel, Switzerland), 5(1), 2. https://doi.org/10.3390/pathogens5010002
- Ouyang, J., Yang, Y., Guo, X., Li, H., & Zhang, Q. (2018). Diagnostic accuracy of sTREM-1 for abdominal and postoperative infections: A meta-analysis. Journal of Critical Care, 45, 140–147.
https://doi.org/10.1016/j.jcrc.2018.02.009 - Siskind, S., Brenner, M., & Wang, P. (2022). TREM-1 Modulation Strategies for Sepsis. Frontiers in immunology, 13, 907387. https://doi.org/10.3389/fimmu.2022.907387
- Su, L., Liu, D., Chai, W., Liu, D., & Long, Y. (2016). Role of sTREM-1 in predicting mortality of infection: a systematic review and meta-analysis. BMJ open, 6(5), e010314. https://doi.org/10.1136/bmjopen-2015-010314
- Whelan, S., Lucey, B., & Finn, K. (2023). Uropathogenic Escherichia coli (UPEC)-Associated Urinary Tract Infections: The Molecular Basis for Challenges to Effective Treatment. Microorganisms, 11(9), 2169. https://doi.org/10.3390/microorganisms11092169