ArticlePLoS neglected tropical diseases2008
Human TLR1 deficiency is associated with impaired mycobacterial signaling and protection from leprosy reversal reaction.
Article in PLoS neglected tropical diseases, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
70 citing papers in PubMed, 143 citations in OpenAlex.
- Pleiotropic effects for Parkin and LRRK2 in leprosy type-1 reactions and Parkinson's disease.Proceedings of the National Academy of Sciences of the United States of America · 2019Trial
- Endosome restricted human TLR1 polymorphism highlights a role for MyD88 in Pam3CSK4 detection.PloS one · 2026Article
- Borderline Lepromatous Leprosy With Type 1 Reaction: A Challenging Diagnostic Case.Clinical case reports · 2024Article
- Prediction of the occurrence of leprosy reactions based on Bayesian networks.Frontiers in medicine · 2023Article
- Interplay among differential exposure toFrontiers in immunology · 2023Article
- A comprehensive analysis of the circRNA-miRNA-mRNA network in osteocyte-like cell associated with Mycobacterium leprae infection.PLoS neglected tropical diseases · 2022Article
- Toll-Like Receptor Signaling and Its Role in Cell-Mediated Immunity.Frontiers in immunology · 2022Review
- Genetic polymorphisms of toll-like receptors in leprosy patients from southern Brazil.Frontiers in genetics · 2022Article
- A Review of Human Coronaviruses' Receptors: The Host-Cell Targets for the Crown Bearing Viruses.Molecules (Basel, Switzerland) · 2021Review
- SARS-CoV-2 S glycoprotein binding to multiple host receptors enables cell entry and infection.Glycoconjugate journal · 2021Review
- TLRs in Mycobacterial Pathogenesis: Black and White or Shades of Gray.Current microbiology · 2021Review
- Can SARS-CoV-2 Virus Use Multiple Receptors to Enter Host Cells?International journal of molecular sciences · 2021Review
- Host-Related Laboratory Parameters for Leprosy Reactions.Frontiers in medicine · 2021Review
- Review
- Genetics of leprosy: today and beyond.Human genetics · 2020Review
- Exonic sequencing identifies TLR1 genetic variation associated with mortality in Thais with melioidosis.Emerging microbes & infections · 2019Article
- Polymorphisms in toll-like receptor (Journal of genetics · 2018Article
- Skin and Soft Tissue Infections Due to Nontuberculous Mycobacteria.Current infectious disease reports · 2018Review
- Innate Immune Responses in Leprosy.Frontiers in immunology · 2018Review
- Genetic polymorphisms of the IL6 and NOD2 genes are risk factors for inflammatory reactions in leprosy.PLoS neglected tropical diseases · 2017Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Toll-like receptors (TLRs) are important regulators of the innate immune response to pathogens, including Mycobacterium leprae, which is recognized by TLR1/2 heterodimers. We previously identified a transmembrane domain polymorphism, TLR1_T1805G, that encodes an isoleucine to serine substitution and is associated with impaired signaling. We hypothesized that this TLR1 SNP regulates the innate immune response and susceptibility to leprosy. In HEK293 cells transfected with the 1805T or 1805G variant and stimulated with extracts of M. leprae, NF-kappaB activity was impaired in cells with the 1805G polymorphism. We next stimulated PBMCs from individuals with different genotypes for this SNP and found that 1805GG individuals had significantly reduced cytokine responses to both whole irradiated M. leprae and cell wall extracts. To investigate whether TLR1 variation is associated with clinical presentations of leprosy or leprosy immune reactions, we examined 933 Nepalese leprosy patients, including 238 with reversal reaction (RR), an immune reaction characterized by a Th1 T cell cytokine response. We found that the 1805G allele was associated with protection from RR with an odds ratio (OR) of 0.51 (95% CI 0.29-0.87, p = 0.01). Individuals with 1805 genotypes GG or TG also had a reduced risk of RR in comparison to genotype TT with an OR of 0.55 (95% CI 0.31-0.97, p = 0.04). To our knowledge, this is the first association of TLR1 with a Th1-mediated immune response. Our findings suggest that TLR1 deficiency influences adaptive immunity during leprosy infection to affect clinical manifestations such as nerve damage and disability.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.