Polymorphisms in Toll-Like Receptors 2, 4, and 9 Are Highly Associated with Hearing Loss in Survivors of Bacterial Meningitis

Well, Gijs Th. J. van; Sanders, Marieke S.; Ouburg, Sander; Furth, A. Marceline van; Morré, Servaas A.

doi:10.1371/journal.pone.0035837

Cited by 37 publications

(45 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The authors of only three studies have reported an association between TLR9 gene polymorphisms and the development of bacterial meningitis (Sanders et al, 2011;Sanders et al, 2012;van Well et al, 2012). The association between TLR9 gene polymorphisms and susceptibility to meningococcal meningitis was investigated in a study by van Well et al (2012); they found that the TLR9-1237 gene polymorphism increased the risk of hearing loss in patients with bacterial meningitis.…”

Section: Discussionmentioning

confidence: 99%

“…The association between TLR9 gene polymorphisms and susceptibility to meningococcal meningitis was investigated in a study by van Well et al (2012); they found that the TLR9-1237 gene polymorphism increased the risk of hearing loss in patients with bacterial meningitis. Sanders et al (2012) revealed that the TLR9-1237 gene polymorphism plays a protective role in the development and severity of meningococcal meningitis.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Association between Toll-like receptor 9 gene polymorphisms and risk of bacterial meningitis in a Chinese population

Xh¹,

Hp²,

Fj³

2016

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. We determined whether two common single nucleotide polymorphisms (SNPs) in the Toll-like receptor 9 gene (TLR9) (TLR9+2848 rs352140 and TLR9-1237 rs5743836) influenced susceptibility to bacterial meningitis in a Chinese population. The study comprised 126 patients with bacterial meningitis and 252 control subjects, all of whom were recruited from the Tuberculosis Hospital of Shanxi Province. Genotyping of TLR9+2848 rs352140 and TLR9-1237 rs5743836 was performed by polymerase chain reaction coupled with restriction fragment length polymorphism. Using logistic regression analysis, we found that individuals with the AA genotype were associated with an increased risk of bacterial meningitis compared with those with the GG genotype (OR = 0.43, 95%CI = 0.19-0.95; P = 0.03). In a recessive model, the AA genotype was correlated with an elevated risk of bacterial meningitis compared with the GG+GA genotype (OR = 0.49, 95%CI = 0.22-0.99; P = 0.04). However, no significant differences were observed in the association between the TLR9-1237 rs5743836 polymorphism and the risk of bacterial meningitis in the codominant, dominant, or recessive models. In conclusion, the results of our study suggest an association between the TLR9+2848 polymorphism and a reduced risk of bacterial meningitis in the codominant and recessive models.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Association between Toll-like receptor 9 gene polymorphisms and risk of bacterial meningitis in a Chinese population

Xh¹,

Hp²,

Fj³

2016

Genet. Mol. Res.

View full text Add to dashboard Cite

show abstract

“…In addition, TLR2 surface expression itself is up-regulated by NM and its PorB but not by NL and its PorB, providing an additional feedback loop for enhancing cell activation and possibly internalization of invasive strains, but not carriage and commensal strains that express other PorB variants. Lastly, analysis of TLR polymorphisms incidence in humans indicates a potential correlation between TLR signaling and meningococcal pathology, by increased risk of infection and susceptibility to NM with TLR2, TLR4 and TLR9 polymorphisms [48-51]. …”

Section: Discussionmentioning

confidence: 99%

Neisseriae internalization by epithelial cells is enhanced by TLR2 stimulation

Toussi

Wetzler

Liu

et al. 2016

Microbes and Infection

View full text Add to dashboard Cite

N. meningitidis (NM) is an opportunistic gram-negative human pathogen that colonizes the human nasopharyngeal epithelium. Asymptomatic carriage is common, but some meningococcal strains can invade nasopharyngeal epithelial cells and proceed to cause severe and often fatal infections. Invasion is predominantly driven by expression of bacterial virulence factors and host cell cognate receptors for bacterial recognition. Porins are among the Neisserial components involved in host cell activation and bacterial internalization processes. Similar to other virulence factors, porins present antigenic and structure variability among strains. Such sequence variability in the surface-exposed loop regions has been correlated to bacterial invasiveness and to variability in host cell responses via Toll-like receptor 2 (TLR2). Here, we examined whether TLR2 signaling by porins influences recovery of intracellular Neisseriae from epithelial cells in vitro. Our results show that TLR2 stimulation, either by the organism or exogenously, generally enhances Neisseriae internalization by epithelial cells. TLR2-driven intracellular signaling via ERK1/2, JNK and particularly NF-κB plays a role in this process. Based on these results, it is possible that expression of porin sequence variants that strongly induce TLR2 activation may be a mechanism to enhance the invasive features of pathogenic Neisseriae strains.

show abstract

“…bVariations have been reported in Carrasco-Colom et al (2015), Ellis et al (2015), van Well et al (2012) and Yuan et al (2008).…”

Section: Figmentioning

confidence: 99%

Variation of 46 Innate Immune Genes Evaluated for their Contribution in Pneumococcal Meningitis Susceptibility and Outcome

et al. 2016

View full text Add to dashboard Cite

Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Early recognition of the pathogen and subsequent innate immune response play a vital role in disease susceptibility and outcome. Genetic variations in innate immune genes can alter the immune response and influence susceptibility and outcome of meningitis disease.Here we conducted a sequencing study of coding regions from 46 innate immune genes in 435 pneumococcal meningitis patients and 416 controls, to determine the role of genetic variation on pneumococcal meningitis susceptibility and disease outcome.Strongest signals for susceptibility were rs56078309 CXCL1 (p = 4.8e − 04) and rs2008521 in CARD8 (p = 6.1e − 04). For meningitis outcome the rs2067085 in NOD2 (p = 5.1e − 04) and rs4251552 of IRAK4 were the strongest associations with unfavorable outcome (p = 6.7e − 04). Haplotype analysis showed a haplotype block, determined by IRAK4 rs4251552, significantly associated with unfavorable outcome (p = 0.004). Cytokine measurements from cerebrospinal fluid showed that with the IRAK4 rs4251552 G risk allele had higher levels of IL-6 compared to individuals with A/A genotype (p = 0.04).We show that genetic variation within exons and flanking regions of 46 innate immunity genes does not yield significant association with pneumococcal meningitis. The strongest identified signal IRAK4 does imply a potential role of genetic variation in pneumococcal meningitis.

show abstract

Polymorphisms in Toll-Like Receptors 2, 4, and 9 Are Highly Associated with Hearing Loss in Survivors of Bacterial Meningitis

Cited by 37 publications

References 49 publications

Association between Toll-like receptor 9 gene polymorphisms and risk of bacterial meningitis in a Chinese population

Association between Toll-like receptor 9 gene polymorphisms and risk of bacterial meningitis in a Chinese population

Neisseriae internalization by epithelial cells is enhanced by TLR2 stimulation

Variation of 46 Innate Immune Genes Evaluated for their Contribution in Pneumococcal Meningitis Susceptibility and Outcome

Contact Info

Product

Resources

About