Gene Polymorphisms of TLR2 Subfamily and Bacterial Meningitis in Angolan Children

TL;DR

This study explores how genetic variations in TLR2 and TLR10 genes affect susceptibility to bacterial meningitis and coexisting infections in Angolan children.

Contribution

The study identifies specific gene polymorphisms in TLR2 and TLR10 associated with reduced risk of coexisting infections in children with bacterial meningitis.

Findings

Patients with a TLR2 rs111200466 variant had lower risk of coexisting infections, especially pneumonia.

A combination of TLR2 variant and TLR10 wildtype genotypes was linked to protection against coexisting pneumonia.

Abstract

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.