Toll-like receptor 1 variations influence susceptibility and immune response to Mycobacterium tuberculosis

Dittrich, Nickel; Berrocal-Almanza, Luis C; Thada, Shruthi; Goyal, Surabhi; Slevogt, Hortense; Gaddam, Sumanlatha; Hussain, Abid; Sur, Saubashya; Burkert, Sanne; Oh, Djin-Ye; Vijayalakshmi, V.; Schumann, Ralf R.; Conrad, Melanie L.

doi:10.1016/j.tube.2015.02.045

Cited by 39 publications

(29 citation statements)

References 39 publications

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“…Interruption of the lipoprotein biosynthesis pathway by deletion of lspA has led to severe attenuation of the bacilli in mice indicating that correct maturation of mycobacterial lipoproteins eventually affecting their localization is essential for infection of the host . Clinical relevance of the lipid anchor in M. tuberculosis infection was indicated when a study in India recently identified that individuals with a single nucleotide polymorphism leading to 248N in the TLR‐1 receptor amino acid sequence have a lower risk of developing tuberculosis than individuals with 248S . In silico analysis of the receptor's structure revealed an additional small cavity in TLR‐1 248N which is not present in TLR‐1 248S and which could bind part of the lipid anchor of lipoproteins.…”

Section: Lipoproteins In M Tuberculosis Virulencementioning

confidence: 99%

“…In silico analysis of the receptor's structure revealed an additional small cavity in TLR‐1 248N which is not present in TLR‐1 248S and which could bind part of the lipid anchor of lipoproteins. Cells with the TLR‐1 248N receptor showed an increased TNF‐α secretion and higher NF‐κB activation upon stimulation with M. tuberculosis lysates, indicating that the TLR‐1 248N receptor better recognizes lipoproteins, thereby conferring improved protection against M. tuberculosis .…”

Section: Lipoproteins In M Tuberculosis Virulencementioning

confidence: 99%

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Mycobacterium tuberculosis lipoproteins in virulence and immunity – fighting with a double‐edged sword

Becker

Sander

2016

FEBS Letters

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Bacterial lipoproteins are secreted membrane‐anchored proteins characterized by a lipobox motif. This lipobox motif directs post‐translational modifications at the conserved cysteine through the consecutive action of three enzymes: Lgt, LspA and Lnt, which results in di‐ or triacylated forms. Lipoproteins are abundant in all bacteria including Mycobacterium tuberculosis and often involved in virulence and immunoregulatory processes. On the one hand, disruption of the biosynthesis pathway of lipoproteins leads to attenuation of M. tuberculosis in vivo, and mycobacteria deficient for certain lipoproteins have been assessed as attenuated live vaccine candidates. On the other hand, several mycobacterial lipoproteins form immunodominant antigens which promote an immune response. Some of these have been explored in DNA or subunit vaccination approaches against tuberculosis. The immune recognition of specific lipoproteins, however, might also benefit long‐term survival of M. tuberculosis through immune modulation, while others induce protective responses. Exploiting lipoproteins as vaccines is thus a complex matter which requires deliberative investigation. The dual role of lipoproteins in the immunity to and pathogenicity of mycobacteria is discussed here.

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Section: Lipoproteins In M Tuberculosis Virulencementioning

confidence: 99%

Section: Lipoproteins In M Tuberculosis Virulencementioning

confidence: 99%

Mycobacterium tuberculosis lipoproteins in virulence and immunity – fighting with a double‐edged sword

Becker

Sander

2016

FEBS Letters

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“…Similarly, SNP rs3764880A/G (Met1Val) in TLR8 was confirmed to be associated with TB and with bacterial loads in a Pakistani population . In contrast, it was reported that the minor allele A of the non‐synonymous SNP rs4833095G/A ( TLR1‐248 Ser/Asn ) was associated with TB protection in an Indian cohort consisting of 206 TB patients and 239 healthy controls . Further in vitro experiments showed that the minor allele rs4833095A ( TLR1‐248Asn ) contributes to increased TNF production of peripheral blood mononuclear cells (PBMC) and to higher NF‐kB expression in HEK cells when PBMC and HEK cells were stimulated with a M. tuberculosis lysate.…”

Section: Candidate Gene Studies In Tuberculosismentioning

confidence: 98%

“…Further in vitro experiments showed that the minor allele rs4833095A ( TLR1‐248Asn ) contributes to increased TNF production of peripheral blood mononuclear cells (PBMC) and to higher NF‐kB expression in HEK cells when PBMC and HEK cells were stimulated with a M. tuberculosis lysate. SNP rs4833095G/A may affect the TLR1 structure, which in turn influences the innate immune response to M. tuberculosis .…”

Section: Candidate Gene Studies In Tuberculosismentioning

confidence: 99%

Human genetic factors in tuberculosis: an update

Tong

Velavan

Thye

et al. 2017

Tropical Med Int Health

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Tuberculosis (TB) is a major threat to human health, especially in many developing countries. Human genetic variability has been recognised to be of great relevance in host responses to Mycobacterium tuberculosis infection and in regulating both the establishment and the progression of the disease. An increasing number of candidate gene and genome-wide association studies (GWAS) have focused on human genetic factors contributing to susceptibility or resistance to TB. To update previous reviews on human genetic factors in TB we searched the MEDLINE database and PubMed for articles from 1 January 2014 through 31 March 2017 and reviewed the role of human genetic variability in TB. Search terms applied in various combinations were 'tuberculosis', 'human genetics', 'candidate gene studies', 'genome-wide association studies' and 'Mycobacterium tuberculosis'. Articles in English retrieved and relevant references cited in these articles were reviewed. Abstracts and reports from meetings were also included. This review provides a recent summary of associations of polymorphisms of human genes with susceptibility/resistance to TB.

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“…TLR1 rs4833095 was also linked with risk of Crohn's and ulcerative colitis diseases [20]. Functional studies by Dittrich et al showed the association of rs4833095 with tuberculosis protection in India [21]. But recent meta analysis by Schurz et al indicated that rs4833095 variant was not correlated with tuberculosis [22].…”

Section: Introductionmentioning

confidence: 99%

TLR1 polymorphism rs4833095 as a risk factor for IgA nephropathy in a Chinese Han population: A case-control study

Gao

Wei

et al. 2016

Oncotarget

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Toll-like receptors (TLRs) are a family of transmembrane receptors, and play a vital role in recognizing invading pathogens and activating innate immunity. Previous studies indicated that TLR1 single nucleotide polymorphisms (SNPs) might be associated with the risk of IgA nephropathy (IgAN). This study aims to investigate the relationship between TLR1 SNPs (rs4833095 and rs5743557) and IgAN in a Chinese Han population. This case-control study included 351 patients with IgAN and 310 healthy controls. Two SNPs (rs4833095 and rs5743557) of TLR1 were genotyped by Sequenom MassARRAY. Odds ratios (OR) with 95% confidence intervals (CI) were used to assess the relationship with IgAN. We found that both allele and genotype frequencies of rs5743557 were not associated with IgAN risk. Rs4833095 increased IgAN risk compared with controls in the allele, dominant and log-additive models (P = 0.04, 0.04 and 0.03, respectively). Further haplotype analysis revealed that the Trs4833095Trs5743557 haplotype may be a risk factor for IgAN (OR = 1.28; 95% CI = 1.01–1.63; P = 0.046). Furthermore, rs4833095 was associated with Lee's grades (OR = 1.75; 95% CI = 1.03–2.96; P = 0.04). However, there was no significant association between the genotype distributions of rs5743557 and clinical parameters of IgAN such as gender, 24 hour urine protein, blood pressure, and Lee's grades. Taken together, these findings suggest that the TLR1 rs4833095 polymorphism may play a role in the development and progression of IgAN.

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Toll-like receptor 1 variations influence susceptibility and immune response to Mycobacterium tuberculosis

Cited by 39 publications

References 39 publications

Mycobacterium tuberculosis lipoproteins in virulence and immunity – fighting with a double‐edged sword

Mycobacterium tuberculosis lipoproteins in virulence and immunity – fighting with a double‐edged sword

Human genetic factors in tuberculosis: an update

TLR1 polymorphism rs4833095 as a risk factor for IgA nephropathy in a Chinese Han population: A case-control study

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