The role of soluble toll-like receptor-2 and 4 in children with pneumonia: a combined analysis of saliva and serum samples


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Necipoglu O., Demir O. O., AYKAÇ K., KARAHAN S., CENGİZ A. B., Aydin M., ...More

Frontiers in Immunology, vol.17, 2026 (SCI-Expanded, Scopus) identifier identifier

  • Publication Type: Article / Article
  • Volume: 17
  • Publication Date: 2026
  • Doi Number: 10.3389/fimmu.2026.1657027
  • Journal Name: Frontiers in Immunology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, MEDLINE, Directory of Open Access Journals
  • Keywords: cytokine, disease severity, lower respiratory tract infection, pediatrics, SARS-CoV-2
  • Hacettepe University Affiliated: Yes

Abstract

Background: Since rapid and accurate diagnosis of pneumonia and determination of its severity remain challenging, particularly in childhood, we aimed to evaluate the role of toll-like receptors (TLR) in pneumonia, which has been limited in animal and adult studies. Methods: In this study, TLR-2, TLR-4, interleukin (IL)-1β, IL-4, IL-6, IL-10, interferon (IFN)-α, and tumor necrosis factor (TNF)-α levels were measured in serum samples of n = 67 pediatric patients with community acquired pneumonia (CAP) (43 inpatients and 24 outpatients) and 22 healthy pediatric controls. Saliva samples of n = 30 pediatric patients with CAP (19 inpatients and 11 outpatients) and 19 healthy pediatric controls were also investigated to analyze the expression of these cytokines and TLRs. Results: In saliva samples taken at the time of diagnosis, threshold levels of TLR-2 were 1.16 2-ΔΔCt and of TLR-4 1.28 2-ΔΔCt differentiating patients with and without pneumonia. The sensitivity of salivary TLR-2 and TLR-4 tests were found to be 0.80 and 0.86, respectively. In serum samples, soluble TLR-2 and TLR-4, IL-1β, IL-4, IL-6, Il-10, IFN-α, and TNF-α levels were significantly decreased in patients with coronavirus disease-19 (COVID-19) as compared with other viruses (p < 0.05 in each). Only one mortal case was present in the inpatient group during the study period. Conclusion: This study demonstrates that salivary TNF-α, soluble TLR-2 and TLR-4 may serve as promising non-invasive biomarkers for diagnosing and stratifying pediatric pneumonia.