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Gene Polymorphisms of TLR2 Subfamily and Bacterial Meningitis in Angolan Children
Johanna Teräsjärvi1, Elina Tenhu1, Manuel Leite Cruzeiro2
1Infection and Immunity, Institute of Biomedicine, University of Turku, 20520 Turku, Finland.
Background/Objectives:
Bacterial meningitis is a severe disease with a fatality rate of 5-50%. It is mainly caused by Streptococcus pneumoniae or Neisseria meningitidis, which can also cause simultaneous infections outside the central nervous system. Toll-like receptors (TLRs) have an important role in the innate immune system. The TLR2 subfamily comprises the four highly homologous members TLR1, TLR2, TLR6, and TLR10, which also have an important immunomodulatory role in infectious diseases.
Methods:
The study cohort consists of 190 bacterial meningitis patients aged 1 to 147 months from randomized clinical trials and 268 controls from Luanda, Angola. Polymorphisms of TLR2 (rs111200466) and TLR10 (rs10856837 and rs11096956) were determined using PCR-based methods and Sanger sequencing. The genotyping results were analyzed together with clinical data to determine whether gene polymorphisms of TLR2 and TLR10 are associated with susceptibility and outcome of bacterial meningitis in Angolan children.
Results:
At admission and during hospitalization, patients with pneumococcal meningitis carrying a variant (ins/del or del/del) of TLR2 rs111200466 had a significantly lower risk of coexisting infections (OR 0.27; 95% CI 0.11-0.65; p = 0.004), particularly pneumonia (OR 0.18; 95% CI 0.06-0.49; p = 0.001). In addition, haplotype analysis demonstrated that a variant genotype of TLR2 rs111200466 together with a wildtype of TLR10 SNPs (rs10856837 and rs11096956) may protect against coexisting pneumonia (OR 0.2; 95% CI 0.06-0.6; p = 0.007).
Conclusions:
This study suggests an association between coexisting infection and genetic variation in TLR2 and TLR10 of bacterial meningitis in Angolan children.
Insights
Genetic variations in Toll-like receptors (TLRs) 2 and 10 may influence the risk of coexisting infections in Angolan children with bacterial meningitis. Specifically, TLR2 variants appear protective against pneumonia in pneumococcal meningitis cases.
Area of Science:
- Immunology
- Genetics
- Infectious Diseases
Background:
- Bacterial meningitis, a severe condition with high fatality rates, is often caused by Streptococcus pneumoniae or Neisseria meningitidis.
- Toll-like receptors (TLRs), particularly the TLR2 subfamily (TLR1, TLR2, TLR6, TLR10), play a crucial role in the innate immune response to infections.
Purpose of the Study:
- To investigate the association between genetic polymorphisms in TLR2 and TLR10 and the susceptibility and outcome of bacterial meningitis in Angolan children.
- To determine if specific TLR gene variants influence the occurrence of coexisting infections in pediatric bacterial meningitis patients.
Main Methods:
- Genotyping of TLR2 (rs111200466) and TLR10 (rs10856837, rs11096956) polymorphisms using PCR and Sanger sequencing.
- Analysis of genotyping results alongside clinical data from 190 bacterial meningitis patients and 268 controls in Luanda, Angola.
Main Results:
- Patients with pneumococcal meningitis and a variant TLR2 rs111200466 genotype showed a significantly reduced risk of coexisting infections, especially pneumonia.
- Haplotype analysis indicated that a combination of variant TLR2 rs111200466 and wildtype TLR10 SNPs may offer protection against coexisting pneumonia.
Conclusions:
- Genetic variations in TLR2 and TLR10 are associated with coexisting infections in Angolan children diagnosed with bacterial meningitis.
- These findings highlight the potential role of specific TLR gene polymorphisms in modulating the immune response and clinical outcomes of bacterial meningitis.
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