Gene Polymorphisms of TLR4 and TLR9 and Haemophilus influenzae Meningitis in Angolan Children

Abstract

Bacterial meningitis (BM) is a severe disease caused by various bacterial pathogens. Toll-like receptors (TLRs) protect humans from invading pathogens. In this study, we determined whether single nucleotide polymorphisms (SNPs) of TLR4 and TLR9 are associated with susceptibility to and outcome of BM in Angolan children. Samples were taken from 241 patients and 265 age-matched ethnic controls. The SNPs TLR4 rs4986790 (896A > G) and TLR9 rs187084 (−1486T > C) were determined by high-resolution melting analysis (HRMA). The frequency of variant genotypes in TLR4 was significantly higher in patients with Haemophilus influenzae meningitis than controls (odds ratio (OR), 2.5; 95% confidence interval (CI), 1.2–5.4; p = 0.021), whereas the frequency of variant genotypes in TLR9 was significantly lower in patients with H. influenzae meningitis than controls (OR, 0.4; 95% CI, 0.2–0.9; p = 0.036). No such differences were found with other causative pathogens, such as Streptococcus pneumoniae and Neisseria meningitidis. At the time of discharge, patients with meningitis caused by Gram-negative bacteria who were carriers of variant TLR4 genotypes had a higher risk of ataxia (OR, 12.91; 95% CI, 1.52–109.80; p = 0.019) and other neurological sequelae (OR, 11.85; 95% CI, 1.07–131.49; p = 0.044) than those with the wild-type TLR4 genotype. Our study suggests an association between H. influenzae meningitis and genetic variation between TLR4 and TLR9 in Angolan children.

Follow-up evaluation of the immunological status of children admitted for acute cerebral nervous system infections: a retrospective study

“…Interestingly, Native Americans, Native Alaskans, and African Americans that experience higher rates of invasive bacterial infections due to HI and SP, also show an increased prevalence of congenital immunodeficiencies (such as the Common Variable or Severe Combined Immuno-Deficiency). It is not yet clear whether Toll-Like Receptors 2, 4, and 9 polymorphisms may predict both susceptibility and unfavourable course of bacterial meningitis caused by SP or NM [6][7][8][9][10]. It has, however been demonstrated that TLR-triggered cytokine secretion is involved in the pathogenesis of meningococcal disease [11].…”

Gene polymorphisms of TLR10: effects on bacterial meningitis outcomes in Angolan children

“…In addition, 133 age‐ and ethnicity‐matched controls were enrolled between 2008 and 2017. Patients and controls are described elsewhere in further detail [16].…”

“…CSF was cultured on blood and chocolate agar plates, and bacteria were identified by Gram stain or standard bacteriological phenotypic methods. Detailed information on the laboratory methods were reported elsewhere [16].…”

“…Samples were collected using a dried blood spot (DBP) collection card (PerkinElmer 226 Sample Collection Device, PerkinElmer, Waltham, MA, USA) and SK‐1S DNA buccal swabs (Isohelix, Harrietsham, Kent, UK). DNA from samples was extracted using the QIAamp ® mini DNA extraction kit (Qiagen, Hilden, Germany) [16].…”

From Immunity to Neurogenesis: Toll-like Receptors as Versatile Regulators in the Nervous System

“…On the other hand, polymorphisms of TLRs are involved in the susceptibility to infections; in this context, the TLR2 2477G/A polymorphism contributes to an increased risk of pneumococcal meningitis in the Caucasian population [ 138 ]. In Angolan children, the single nucleotide polymorphism TLR4 rs4986790 increases the susceptibility to bacterial meningitis caused by Haemophilus influenzae, the risk of ataxia, and neurological sequelae, while TLR9 rs187084 decreases the risk [ 139 ]. A meta-analysis revealed that the TLR9 polymorphism rs352140 is associated with a decreased risk of bacterial meningitis [ 140 ].…”