ASSOCIATION OF TLR2, TLR4, AND TLR6 GENE POLYMORPHISMS WITH STREPTOCOCCUS PNEUMONIAE COLONIZATION IN WORKERS OF A METALLURGICAL ENTERPRISE
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Abstract
Workers employed in ferrous metallurgy enterprises are exposed to industrial aerosols of organic and inorganic origin, which may impair innate immune mechanisms and increase the incidence of respiratory infections. Genetic variability in the Toll-like receptor system may influence susceptibility to pneumococcal colonization. However, data on the prevalence of functional polymorphisms in TLR2, TLR4, and TLR6 among workers in metallurgical industries remain limited.
The aim of this study was to evaluate the association between TLR gene polymorphisms and Streptococcus pneumoniae colonization in workers of a ferrous metallurgy enterprise.
Materials and Methods. A total of 136 apparently healthy workers from a ferrous metallurgy enterprise were examined. Genotyping of TLR2 (rs5743708), TLR4 (rs4986790), and TLR6 (rs5743810) polymorphisms was performed using real-time PCR. Genotype frequencies were compared according to the presence of S. pneumoniae colonization. Statistical analysis included the χ² test, odds ratio estimation, and calculation of 95% confidence intervals.
Results. The distribution of genotype frequencies did not differ between workers from different production units. The TLR4 polymorphism demonstrated a significant association with S. pneumoniae carriage: the minor G allele was detected 3.5 times more frequently among carriers (28.6% vs 8.2%; OR = 4.48), and the heterozygous A/G genotype was associated with a 6.8-fold increased risk of colonization. No statistically significant associations were observed for TLR2 and TLR6, although biologically plausible trends were noted.
Conclusion. The polymorphic variant of TLR4 represents a genetic marker of susceptibility to asymptomatic S. pneumoniae colonization among workers of the studied enterprise.
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Riccò M, Ferraro P, Zaffina S, Camisa V, Marchesi F, Gori D. Vaccinating Welders against Pneumococcus: Evidence from a Systematic Review and Meta-Analysis. Vaccines. 2023; 11(9): 1495. doi: 10.3390/vaccines11091495
Bushueva TV, Karpova EP, Roslaya NA, Gurvich VB, Labzova AK, Gribova YuV. Immune response status and development of Streptococcus pneumoniae carriage as health risk factors for workers engaged in coke production and basic oxygen steelmaking. Health risk analysis. 2023; (4): 116-123. Russian (Бушуева Т.В., Карпова Е.П., Рослая Н.А., Гурвич В.Б., Лабзова А.К., Грибова Ю.В. Состояние иммунного ответа и формирование носительства Streptococcus pneumoniae как факторы риска здоровью работников коксохимического и конвертерного производства //Анализ риска здоровью. 2023. № 4. С. 116-123.) doi: 10.21668/health.risk/2023.4.11
Torén K, Blanc PD, Naidoo R, Murgia N, Stockfelt L, Schiöler L. Cumulative Occupational Exposure to Inorganic Dust and Fumes and Invasive Pneumococcal Disease with Pneumonia. Int Arch Occup Environ Health. 2022; 95: 1797-1804. doi: 10.1007/s00420-022-01888-y
Torén K, Naidoo RN, Blanc PD. Pneumococcal Pneumonia on the Job: Uncovering the Past Story of Occupational Exposure to Metal Fumes and Dust. Am J Ind Med. 2022; 65: 517-524. doi: 10.1002/ajim.23355
Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing (Rospotrebnadzor). On the state of sanitary and epidemiological welfare of the population in the Russian Federation in 2024: State report. Moscow, 2025. Russian (О состоянии санитарно-эпидемиологического благополучия населения в Российской Федерации в 2024 году: Государственный доклад. М.: Федеральная служба по надзору в сфере защиты прав потребителей и благополучия человека, 2025. 424 с.) URL: https://www.rospotrebnadzor.ru/documents/details.php?ELEMENT_ID=30171 (дата обращения: 09.11.2025)
Duan T, Du Y, Xing C, Wang HY, Wang RF. Toll-like receptor signaling and its role in cell-mediated immunity. Front Immunol. 2022; 13: 812774. doi: 10.3389/fimmu.2022.812774
Sekar PKC, Veerabathiran R. Assessing the Impact of TLR4 rs4986790 Polymorphism on Bacterial Meningitis Risk: A Systematic Review and Meta-Analysis. Ann Indian Acad Neurol. 2024; 27(6): 629-637. doi: 10.4103/aian.aian_443_24
Behairy MY, Abdelrahman AA, Toraih EA, Ibrahim EEDA, Azab MM, Sayed AA, Hashem HR. Investigation of TLR2 and TLR4 Polymorphisms and Sepsis Susceptibility: Computational and Experimental Approaches. Int J Mol Sci. 2022; 23(18): 10982. doi: 10.3390/ijms231810982
Salamaikina S, Karnaushkina M, Korchagin V, Litvinova M, Mironov K, Akimkin V. TLRs Gene Polymorphisms Associated with Pneumonia before and during COVID-19 Pandemic. Diagnostics (Basel). 2023; 13(1): 121. doi: 10.3390/diagnostics13010121
Abd El-Hamid SM, Abd AA, Elalim EN, Moustafa S, Moazen EM, Abdo WH. Impact of Toll-like receptor 2 (rs5743708) gene polymorphism in pediatric pneumonia: risk and severity. Egypt J Immunol. 2024; 31(3): 48-55. doi: 10.55133/eji.310307
Branger J, Knapp S, Weijer S, Leemans JC, Pater JM, Speelman P. Role of Toll-Like Receptor 4 in Gram-Positive and Gram-Negative Pneumonia in Mice. Infect Immun. 2004; 72(2): 788-794. doi: 10.1128/iai.72.2.788-794.2004
Sánchez-Tarjuelo R, Cortegano I, Manosalva J, Rodríguez M, Ruíz C, Alía M. The TLR4-MyD88 signaling axis regulates lung monocyte differentiation pathways in response to streptococcus pneumoniae. Front Immunol. 2020; 11: 2120. doi: 10.3389/fimmu.2020.02120
Silva MJA, Santana DS, de Oliveira LG, Monteiro EOL, Lima LNGC. The relationship between 896A/G (rs4986790) polymorphism of TLR4 and infectious diseases: A meta-analysis. Front Genet. 2022; 13: 1045725. doi: 10.3389/fgene.2022.1045725
Mhmoud NA. Association of Toll-like Receptors 1, 2, 4, 6, 8, 9 and 10 Genes Polymorphisms and Susceptibility to Pulmonary Tuberculosis in Sudanese Patients. Immunotargets Ther. 2023; 12: 47-75. doi: 10.2147/ITT.S404915
Yuan FF, Marks K, Wong M, Watson S, de Leon E, McIntyre PB, Sullivan JS. Clinical relevance of TLR2, TLR4, CD14 and FcγRIIA gene polymorphisms in Streptococcus pneumoniae infection. Immunol Cell Biol. 2008; 86(3): 268-270. doi: 10.1038/sj.icb.7100155
Varzari A, Deyneko IV, Tudor E, Grallert H, Illig T. Synergistic effect of genetic polymorphisms in TLR6 and TLR10 genes on the risk of pulmonary tuberculosis in a Moldavian population. Innate Immun. 2021; 27(5): 365-376. doi: 10.1177/17534259211029996
Lorenz E, Mira JP, Frees KL, Schwartz DA. Relevance of mutations in the TLR4 receptor in patients with gram-negative septic shock. Arch Intern Med. 2002; 162(9): 1028-1032. doi: 10.1001/archinte.162.9.1028
Moens L, Meyts I. Recent human genetic errors of innate immunity leading to increased susceptibility to infection. Curr Opin Immunol. 2020; 62: 79-90. doi: 10.1016/j.coi.2019.12.004
Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell. 2010; 140(6): 805-820. doi: 10.1016/j.cell.2010.01.022
Ma K, Guo J, Wang G, Ni Q, Liu X. Toll-Like Receptor 2–Mediated Autophagy Promotes Microglial Cell Death by Modulating the Microglial M1/M2 Phenotype. Inflammation. 2020; 43: 701-711. doi: 10.1007/s10753-019-01152-5