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

**Authors:** Ozlem Necipoglu, Osman Oguz Demir, Kubra Aykac, Sevilay Karahan, Ali Bulent Cengiz, Malik Aydin, Yasemin Ozsurekci

PMC · DOI: 10.3389/fimmu.2026.1657027 · Frontiers in Immunology · 2026-02-13

## TL;DR

This study explores the use of saliva and serum samples to identify biomarkers for diagnosing and assessing the severity of pneumonia in children.

## Contribution

The study introduces salivary TLR-2 and TLR-4 as potential non-invasive biomarkers for pediatric pneumonia diagnosis and severity stratification.

## Key findings

- Salivary TLR-2 and TLR-4 showed high sensitivity for detecting pneumonia in children.
- Serum levels of TLR-2, TLR-4, and several cytokines were significantly lower in children with COVID-19 compared to other viral pneumonias.
- Soluble TLR-2 and TLR-4 in saliva may serve as promising non-invasive biomarkers for pediatric pneumonia.

## Abstract

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.

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.

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.

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.

## Linked entities

- **Genes:** TLR2 (toll like receptor 2) [NCBI Gene 7097], TLR4 (toll like receptor 4) [NCBI Gene 7099], IL1B (interleukin 1 beta) [NCBI Gene 3553], IL4 (interleukin 4) [NCBI Gene 3565], IL6 (interleukin 6) [NCBI Gene 3569], IL10 (interleukin 10) [NCBI Gene 3586], IFN1@ (interferon, type 1, cluster) [NCBI Gene 3438], TNF (tumor necrosis factor) [NCBI Gene 7124]
- **Diseases:** pneumonia (MONDO:0005249), COVID-19 (MONDO:0100096)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** ACE2 (angiotensin converting enzyme 2) [NCBI Gene 59272] {aka ACEH}, TICAM1 (TIR domain containing adaptor molecule 1) [NCBI Gene 148022] {aka IIAE6, MyD88-3, PRVTIRB, TICAM-1, TRIF}, CALCA (calcitonin related polypeptide alpha) [NCBI Gene 796] {aka CALC1, CGRP, CGRP-I, CGRP-alpha, CGRP1, CT}, TLR3 (toll like receptor 3) [NCBI Gene 7098] {aka CD283, IIAE2, IMD83}, TLR-4 [NCBI Gene 100540712], TLR1 (toll like receptor 1) [NCBI Gene 7096] {aka CD281, TIL, TIL. LPRS5, rsc786}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, VTN (vitronectin) [NCBI Gene 7448] {aka V75, VN, VNT}, TRIM63 (tripartite motif containing 63) [NCBI Gene 84676] {aka CMH31, IRF, MURF1, MURF2, RNF28, SMRZ}, ERVK-6 (endogenous retrovirus group K member 6, envelope) [NCBI Gene 64006] {aka ERVK6, HERV-K(C7), HERV-K108, K-Rev, c-orf, cORF}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, TLR6 (toll like receptor 6) [NCBI Gene 10333] {aka CD286}, TLR2 (toll like receptor 2) [NCBI Gene 7097] {aka CD282, TIL4}, IL-10 [NCBI Gene 100303698], TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, IFNA1 (interferon alpha 1) [NCBI Gene 3439] {aka IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, IFNA@}, TLR7 (toll like receptor 7) [NCBI Gene 51284] {aka IMD74, SLEB17, TLR7-like}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, IL-6 [NCBI Gene 100548599], MYD88 (MYD88 innate immune signal transduction adaptor) [NCBI Gene 4615] {aka IMD68, MYD88D, WM1}, TLR10 (toll like receptor 10) [NCBI Gene 81793] {aka CD290}, ACTB [NCBI Gene 100303677], TLR-2 [NCBI Gene 104910743], JUNB (JunB proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 3726] {aka AP-1}, TLR8 (toll like receptor 8) [NCBI Gene 51311] {aka CD288, IMD98, TLR-8, hTLR8}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, IL-1B [NCBI Gene 100034741], CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}
- **Diseases:** bronchopneumonia (MESH:D001996), hypotension (MESH:D007022), acute respiratory distress syndrome (MESH:D012128), fever (MESH:D005334), Pneumonia (MESH:D011014), pneumococcal pneumonia (MESH:D011018), confusion (MESH:D003221), pleural effusion (MESH:D010996), acute lung injury (MESH:D055371), cystic fibrosis (MESH:D003550), lung injury (MESH:D055370), multiorgan failure (MESH:D051437), pulmonary diseases (MESH:D008171), respiratory infection (MESH:D012141), infectious inflammation (MESH:D007249), CAP (MESH:D003147), sepsis (MESH:D018805), Infectious Diseases (MESH:D003141), loss of appetite (MESH:D001068), cytokine storm (MESH:D000080424), primary ciliary dyskinesia (MESH:D002925), rheumatologic disease (MESH:D012216), Tachypnea (MESH:D059246), restlessness (MESH:D011595), infection (MESH:D007239), COVID-19 (MESH:D000086382), bacteremia (MESH:D016470), Running (MESH:D020195), pneumococcal infection (MESH:D011008), immunodeficiency (MESH:D007153), death (MESH:D003643), COVID-19 pneumonia (MESH:D018352), viral (MESH:D014777), leukemia (MESH:D007938), MIS-C (MESH:C000705967)
- **Chemicals:** glycolipids (MESH:D006017), LPS (MESH:D008070), surface (-)
- **Species:** Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Human rhinovirus sp. (species) [taxon 169066], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395]

## Full text

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## Figures

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## References

60 references — full list in the complete paper: https://tomesphere.com/paper/PMC12945803/full.md

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Source: https://tomesphere.com/paper/PMC12945803