Alterations in<i>TLRs</i>as new molecular markers of congenital infections with<i>Human cytomegalovirus</i>?

Wujcicka, Wioletta; Wilczyński, J; Nowakowska, Dorota

doi:10.1111/2049-632x.12083

Cited by 16 publications

(20 citation statements)

References 148 publications

(252 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For instance, TLR2 was been found to functionally recognize HCMV through direct interaction with the envelope tegumental glycoproteins, gB and gH, suggesting that the innate immune response activated by HCMV might be primarily dependent on viral envelope proteins and independent of viral replication in permissive fibroblasts [76]. Moreover, there was a reported interaction of CMV with TLR7 and TLR9 in human plasmacytoid dendritic cells (pDC), suggesting that TLR involvement might also be related to the cell types in which the virus establishes the infection [77]. The downregulation of TLR signaling pathways may help CMV infect pDCs and transfer to endothelial cells and fibroblast during early infection, while activation of TLRs in these cells may increase during viral reactivation at a later stage contributing to SSc disease.…”

Section: Cytomegalovirus Innate Immunity Vasculopathies and Fibrosmentioning

confidence: 99%

Fresh Insights into Disease Etiology and the Role of Microbial Pathogens

Farina

2015

Curr Rheumatol Rep

View full text Add to dashboard Cite

Pathogens have been implicated in the initiation and/or promotion of systemic sclerosis (scleroderma, SSc); however, no evidence was found to substantiate the direct contribution to this disease in past years. Recently, significant advances have been made in understanding the role of the innate immune system in SSc pathogenesis, supporting the idea that pathogens might interact with host innate immune-regulatory responses in SSc. In light of these findings, we review the studies that identified the presence of pathogens in SSc, along with studies on pathogens implicated in driving the innate immune dysregulation in SSc. The goal of this review is to illustrate how these pathogens, specifically viruses, may play important role both as triggers of the innate immune system, and critical players in the development of SSc disease.

show abstract

Section: Cytomegalovirus Innate Immunity Vasculopathies and Fibrosmentioning

confidence: 99%

Fresh Insights into Disease Etiology and the Role of Microbial Pathogens

Farina

2015

Curr Rheumatol Rep

View full text Add to dashboard Cite

show abstract

“…The identified heterozygotes in the range of TLR2 SNP were estimated as 10 times more susceptible to develop the infection. TLR2 molecule was previously reported to be involved in the immune response against HCMV [15, 19–21]. In ectocervical tissue, HCMV infection was blocked by ligands for TLR2 (LTA), as well as TLR9 (CpG) molecules [41].…”

Section: Discussionmentioning

confidence: 99%

“…Several studies reported some involvement of Toll-like receptors (TLRs) in immune response against HCMV [13–15]. Particularly, the TLR2 molecule was shown to support the immunity to the virus [16–18].…”

Section: Introductionmentioning

confidence: 99%

“…In turn, a study with HCMV permissive fibroblasts showed a functional sensing of the virus by TLR2 through direct interaction with viral envelope glycoproteins (gp, g), gB and gH [19]. In human acute monocytic leukemia cell line THP1 and in foreskin fibroblast cell lines, HCMV infection induces the expression of TLR2 , TLR3 and TLR9 genes [15, 18]. In colorectal cancer tissues, HCMV IE1-72 protein expression correlates with TLR2 and TLR4 [20].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

TLR2 2258 G>A single nucleotide polymorphism and the risk of congenital infection with human cytomegalovirus

Wujcicka

Paradowska

Studzińska

et al. 2017

Virol J

Self Cite

View full text Add to dashboard Cite

BackgroundHuman cytomegalovirus (HCMV) is responsible for the most common intrauterine infections, which may be acquired congenitally from infected pregnant woman to fetus. The research was aimed to estimate the role of three single nucleotide polymorphisms (SNPs) located in TLR2 gene, and the common contribution of TLR2, and previously studied TLR4 and TLR9 SNPs, to the occurrence of congenital HCMV infection in fetuses and newborns.MethodsThe study was performed in 20 Polish fetuses and newborns, congenitally infected with HCMV, and in 31 uninfected controls, as well as with participation of pregnant women, the mothers of 16 infected and 14 uninfected offsprings. Genotypes in TLR2 SNPs were determined, using self-designed nested PCR-RFLP assays, and confirmed by sequencing. The genotypes were tested for Hardy-Weinberg (H-W) equilibrium, and for their relationship with the development of congenital cytomegaly, using a logistic regression model. The common influence of TLR2, TLR4 and TLR9 SNPs on the occurrence of congenital disease was estimated by multiple-SNP analysis.ResultsDistribution of the genotypes and alleles in TLR2 1350 T>C and 2029 C>T SNPs was similar between the studied groups of fetuses and neonates. In case of 2258 G>A polymorphism, the GA heterozygotic status was significantly more frequent in the infected cases than among the uninfected individuals (25.0% vs. 3.2%, respectively), and increased the risk of HCMV infection (OR 10.00, 95% CI 1.07–93.44; P ≤ 0.050). Similarly, the A allele within 2258 G>A polymorphism was significantly more frequent among the infected offsprings than in the uninfected ones (12.5% vs. 1.6%; P ≤ 0.050). Complex AA variants for both TLR2 2258 and TLR9 2848 G>A polymorphisms, were estimated to be at increased risk of congenital HCMV infection (OR 11.58, 95% CI 1.19–112.59; P ≤ 0.050). Additionally, significant relationships were observed between the occurrence of complex AA or GA variants for both TLR2 and TLR9 SNPs and the increased viral loads, determined in fetal amniotic fluids and in maternal blood or urine specimens (P ≤ 0.050).ConclusionsAmong various TLR2, TLR4 and TLR9 polymorphisms, TLR2 2258 G>A SNP seems to be an important factor associated with increased risk of congenital HCMV infection in Polish fetuses and neonates.

show abstract

“…Polymorphisms in TLR2 appear to enhance an individual's susceptibility to lytic infection and the development of subsequent pathology [162]. Other authors have reported that TLR polymorphisms or epigenetic changes in the methylation state of their gene promoter regions influence the duration and magnitude of the immune response to HCMV infection [163]. On the other hand, heterozygosity in TLR2 and TLR4 receptors diminishes the risk of infection by this virus in adults [164].…”

Section: Cytomegalovirusmentioning

confidence: 99%

The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability

Morris¹,

Berk

Walder

et al. 2015

Mol Neurobiol

View full text Add to dashboard Cite

Patients who present with severe intractable apparently idiopathic fatigue accompanied by profound physical and or cognitive disability present a significant therapeutic challenge. The effect of psychological counseling is limited, with significant but very slight improvements in psychometric measures of fatigue and disability but no improvement on scientific measures of physical impairment compared to controls. Similarly, exercise regimes either produce significant, but practically unimportant, benefit or provoke symptom exacerbation. Many such patients are afforded the exclusionary, non-specific diagnosis of chronic fatigue syndrome if rudimentary testing fails to discover the cause of their symptoms. More sophisticated investigations often reveal the presence of a range of pathogens capable of establishing life-long infections with sophisticated immune evasion strategies, including Parvoviruses, HHV6, variants of Epstein-Barr, Cytomegalovirus, Mycoplasma, and Borrelia burgdorferi. Other patients have a history of chronic fungal or other biotoxin exposure. Herein, we explain the epigenetic factors that may render such individuals susceptible to the chronic pathology induced by such agents, how such agents induce pathology, and, indeed, how such pathology can persist and even amplify even when infections have cleared or when biotoxin exposure has ceased. The presence of active, reactivated, or even latent Herpes virus could be a potential source of intractable fatigue accompanied by profound physical and or cognitive disability in some patients, and the same may be true of persistent Parvovirus B12 and mycoplasma infection. A history of chronic mold exposure is a feasible explanation for such symptoms, as is the presence of B. burgdorferi. The complex tropism, life cycles, genetic variability, and low titer of many of these pathogens makes their detection in blood a challenge. Examination of lymphoid tissue or CSF in such circumstances may be warranted.

show abstract

Alterations inTLRsas new molecular markers of congenital infections withHuman cytomegalovirus?

Cited by 16 publications

References 148 publications

Fresh Insights into Disease Etiology and the Role of Microbial Pathogens

Fresh Insights into Disease Etiology and the Role of Microbial Pathogens

TLR2 2258 G>A single nucleotide polymorphism and the risk of congenital infection with human cytomegalovirus

The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability

Contact Info

Product

Resources

About