Genetic polymorphisms within the human Toll-like receptor 2 subfamily

2007 ◽  
Vol 35 (6) ◽  
pp. 1445-1448 ◽  
Author(s):  
R.I. Tapping ◽  
K.O. Omueti ◽  
C.M. Johnson
Keyword(s):  
Infectious Disease ◽  
Innate Immune System ◽  
Purifying Selection ◽  
Innate Immune ◽  
Nucleotide Polymorphisms ◽  
Toll Like Receptor ◽  
Selective Force ◽  
Single Nucleotide ◽  
Toll Like Receptor 2

Infectious disease is a formidable selective force in Nature as is evident from the complexity of immune systems across multicellular species. TLRs (Toll-like receptors) constitute central pattern-recognition molecules of the innate immune system that sense bacterial, viral, fungal, protozoan and helminth organisms and activate responses that provide immediate as well as long-term protection for the host. The present article reviews the function and evolution of vertebrate TLRs with an emphasis on the subfamily of receptors comprising human TLR1, 2, 6 and 10. The idea that TLRs undergo strong purifying selection provides the framework for the discussion of single nucleotide polymorphisms, many of which are associated with the incidence of infectious disease.

scholarly journals Relationship between interleukin-18-607C/A gene polymorphism and severity of enterovirus-71 encephalitis in Chinese children

2019 ◽  
Author(s):  
Jie Song ◽  
Yedan Liu ◽  
Zhenghai Qu ◽  
Ya Guo ◽  
Peipei Liu ◽  
...  
Keyword(s):  
Serum Concentration ◽  
Innate Immune System ◽  
Promoter Region ◽  
Enterovirus 71 ◽  
Innate Immune ◽  
Nucleotide Polymorphisms ◽  
Interleukin 18 ◽  
Single Nucleotide ◽  
Ifn Γ ◽  
Infectious Encephalitis

Abstract Background: Interleukin-18 (IL-18), a pro-inflammatory cytokine encoded by IL-18 and known as interferon (IFN)-γ inducing factor, plays an important role in the innate immune system. Single nucleotide polymorphisms (SNPs) of IL-18-607C/A have been reported to be associated with many infectious and immune-related diseases. However, there is no evidence of its association with enterovirus 71 (EV71)-infectious encephalitis. This study aimed to explore the association between the promoter region polymorphisms (-607C/A) of IL-18 and the severity of EV71 encephalitis in Chinese children.Methods: We analyzed the polymorphisms of IL-18-607C/A in 185 EV71-infected patients and 214 controls for genetic association research. Clinical features and auxiliary examination results were collected and compared in the cases. The serum concentration of IFN-γ was detected using enzyme-linked immunosorbent assays (ELISA). Results: The frequency of IL-18-607 AA genotype and allele in EV71-infected patients was significantly higher than that in the controls (32.4% vs 21.5%, P=0.042, 55.1% vs 46.0%, P=0.001). Furthermore, a difference was found in severe EV71 and mild encephalitis cases (53.0% vs 20.5%, P=0.003, 67.3% vs 50%, P=0.016). The serum concentration of IFN-γ in patients with encephalitis was much lower in AA genotypes (106.0±8.9 pg/mL) than in CA and CC genotypes (120.4±8.9 and 128.1±7.5 pg/mL, respectively, P<0.001). The duration of fever and blood glucose level was obviously higher in AA than in CA and CC genotypes.Conclusions: Children with IL-18-607AA genotype were more susceptible to developing severe EV71-associated encephalitis in this study in China.

scholarly journals Polymorphisms of TLR2, TLR4 and TOLLIP and tuberculosis in two independent studies

2020 ◽  
Vol 40 (8) ◽  
Author(s):  
Shouquan Wu ◽  
Xiangmin Liu ◽  
Ling Chen ◽  
Yu Wang ◽  
Miaomiao Zhang ◽  
...  
Keyword(s):  
Protective Factor ◽  
Nucleotide Polymorphisms ◽  
Toll Like Receptor ◽  
Chinese Han ◽  
Single Nucleotide ◽  
Interacting Protein ◽  
Han Population ◽  
Tibetan Population ◽  
Immunity Genes ◽  
Toll Like Receptor 2

Abstract Genetic polymorphisms for tuberculosis (TB) susceptibility have been researched by some studies, but few have studied multiple innate immunity genes associated with TB. Evidence suggests that the toll-like receptor 2, 4 (TLR2, TLR4) and toll interacting protein (TOLLIP) may be associated with TB susceptibility. In this self-validated study, we explored the association between common single nucleotide polymorphisms (SNPs) of TLR2, TLR4 and TOLLIP in the Chinese Han and Tibetan populations. A SNPscan™ method was used to genotype SNPs in the three genes. Multiple logistic regression adjusted by sex and age was used to detect the association between SNPs and TB. In TLR2, rs1898830 was associated with decreased risk against TB in the Chinese Han population, which was validated in the Tibetan population. In TLR4, rs11536889 was a protective factor for TB in the Tibetan population, but not in the Han population. Additionally, in the Tibetan population, we also found that the frequency of genotypes of TOLLIP rs11536889 differs significantly between TB patients and controls. We found rs1898830 in TLR2 was associated with TB susceptibility in both Chinese Han and Tibetan populations while rs11536889 in TLR4 and rs3750920 in TOLLIP were protective factors against TB in the Tibetan population.

scholarly journals The Arg753Gln Polymorphism of Toll-Like Receptor 2 Has a Lower Occurrence in Patients with Syphilis, Suggesting Its Protective Effect in Czech and Slovak Individuals

2020 ◽  
Vol 89 (1) ◽  
pp. e00503-20
Author(s):  
Linda Grillová ◽  
Jana Musilová ◽  
Klára Janečková ◽  
Petra Pospíšilová ◽  
Ivana Kuklová ◽  
...  
Keyword(s):  
Treponema Pallidum ◽  
Signaling Cascade ◽  
Nucleotide Polymorphisms ◽  
Toll Like Receptor ◽  
Healthy Individuals ◽  
Single Nucleotide ◽  
Content Type ◽  
Tlr2 Polymorphism ◽  
History Of ◽  
Toll Like Receptor 2

ABSTRACTSyphilis is a bacterial infection caused by Treponema pallidum subsp. pallidum. Infection with T. pallidum subsp. pallidum and its dissemination lead to the synthesis of proinflammatory cytokines triggered by the interaction of bacterial lipoproteins with Toll-like receptor 2 (TLR2). TLR2 contains several nonsynonymous single-nucleotide polymorphisms that may impact the activation of its signaling cascade and alter the responsiveness to, or the course of, various infectious diseases, including those caused by pathogenic spirochetes. To investigate whether TLR2 polymorphism may influence susceptibility to syphilis, 221 healthy individuals with no history of syphilis (controls) and 137 patients diagnosed with syphilis (cases) were screened for the presence of the Arg753Gln polymorphism in the TLR2 gene (2258G→A; rs5743708). The Arg753Gln variant occurs at a significantly lower frequency in syphilis patients (4 of 137 [3%]) than in controls (24 of 221 [10.9%]). These data suggest that TLR2 Arg753Gln may protect from the development of syphilis due to reduced signaling.

scholarly journals Activation of the Innate Immune System by Treponema denticola Periplasmic Flagella through Toll-Like Receptor 2

2017 ◽  
Vol 86 (1) ◽  
Author(s):  
John Ruby ◽  
Michael Martin ◽  
Michael J. Passineau ◽  
Valentina Godovikova ◽  
J. Christopher Fenno ◽  
...  
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Innate Immune ◽  
Treponema Denticola ◽  
Toll Like Receptor ◽  
Wild Type ◽  
Content Type ◽  
Tnf Α ◽  
Toll Like Receptor 2 ◽  
Periplasmic Flagella

ABSTRACTTreponema denticolais an indigenous oral spirochete that inhabits the gingival sulcus or periodontal pocket. Increased numbers of oral treponemes within this environment are associated with localized periodontal inflammation, and they are also part of an anaerobic polymicrobial consortium responsible for endodontic infections. Previous studies have indicated thatT. denticolastimulates the innate immune system through Toll-like receptor 2 (TLR2); however, the pathogen-associated molecular patterns (PAMPs) responsible forT. denticolaactivation of the innate immune system are currently not well defined. In this study, we investigated the role played byT. denticolaperiplasmic flagella (PF), unique motility organelles of spirochetes, in stimulating an innate immune response. Wild-typeT. denticolastimulated the production of the cytokines tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-6, IL-10, and IL-12 by monocytes from human peripheral blood mononuclear cells, while its isogenic nonmotile mutant lacking PF resulted in significantly diminished cytokine stimulation. In addition, highly purified PF were able to dose dependently stimulate cytokine TNF-α, IL-1β, IL-6, IL-10, and IL-12 production in human monocytes. Wild-typeT. denticolaand the purified PF triggered activation of NF-κB through TLR2, as determined using a variety of TLR-transfected human embryonic 293 cell lines, while the PF-deficient mutants lacked the ability to stimulate, and the complemented PF-positiveT. denticolastrain restored the activation. These findings suggest thatT. denticolastimulates the innate immune system in a TLR2-dependent fashion and that PF are a key bacterial component involved in this process.

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