Abstract

Toll-like receptors (TLRs) play a crucial role in innate immunity, protecting the host from bacterial pathogens. We investigated whether bacterial meningitis (BM) in children was associated with gene polymorphisms in TLR2 (rs3804099), TLR3 (rs3775291 and rs3775290) and TLR9 (rs352139 and rs352140). Blood samples were taken from 218 child patients with confirmed BM and 330 healthy adult controls (HC) and polymorphisms of these genes were analyzed by PCR-based sequencing. For TLR2 rs3804099, frequencies of the minor allele C were markedly higher in patients with severe BM (defined as CSF glucose concentration ≤ 1.5 mmol/L and seizures) than those without (43.5% and 40.1% vs. 30.1% and 29.1%, p = 0.008 and p = 0.016, respectively). For TLR9 rs352139, patients who carried genotype AA and minor allele A developed seizures less often than those without (OR = 0.289, p = 0.003 and OR = 0.568, p = 0.004, respectively). However, for TLR9 rs352140, patients who carried genotype TT and minor allele T developed seizures more often than those without (OR = 3.385, p = 0.004 and OR = 1.767, p = 0.004, respectively). Our finding suggested that genetic variations in TLR2 and TLR9 are associated with severity and prognosis of bacterial meningitis in Chinese children. However, the results should be interpreted with caution since the number of subjects included was limited.

Highlights

  • Early recognition of invading bacteria by TLRs and the shaping of appropriate immune responses are essential for control of bacterial meningitis (BM) development

  • For TLR3 rs3775291, lower frequency of TT genotype in BM patients (3.7%) was found when compared to that of HC (9.1%) (OR = 0.366, 95%confidence interval (CI): 0.162–0.826, P = 0.013)

  • No significant differences were observed. This is the first study carried out in China to show the relationships between TLRs and susceptibility, severity and prognosis of bacterial meningitis in pediatric patients

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Summary

Introduction

Early recognition of invading bacteria by TLRs and the shaping of appropriate immune responses are essential for control of BM development. In human SNPs in TLR9 were associated with meningococcemia and meningococcal meningitis in Dutch children[20,21]. Data from these studies suggest that bacterial infection leads to a TLR-dependent innate response, and functional variations in TLRs can influence susceptibility and outcome of various bacterial infections. A vast number of TLR SNPs have been identified, there is no reported study to investigate the possible associations between the TLR SNPs and susceptibility, severity or prognosis of BM in Chinese children. Candidate SNPs were chosen based on published data of experimental studies in mice and of known genetic variation of TLRs and their possible effects on susceptibility to meningitis in human[14,21,22,23]

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