Genetic variation within TLR10 is associated with Crohn's disease in a New Zealand population.
ABSTRACT Toll-like receptors (TLRs) play an important role in the induction and regulation of the innate immune system and have been implicated in both infectious and inflammatory diseases. Recently the first association of TLR10 with Crohn's disease (CD) was reported. Here, we attempted to validate this association, using a candidate gene single nucleotide polymorphism (SNP) study of TLR10 in CD. We identified tagging SNPs, and genotyped these SNPs in a Caucasian New Zealand dataset consisting of 406 CD patients and 638 controls. In this sample, we were able to demonstrate an association between CD and several different TLR10 SNPs and haplotypes. Phenotypic analysis showed an association with early age at first diagnosis, inflammatory and ileocolonic CD behavior, requirement of bowel resection, and extra intestinal manifestations. This study provides evidence to suggest that genetic variation in TLR10 plays a role in interindividual differences in CD susceptibility and clinical outcome.
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ABSTRACT: Toll-like receptors (TLRs), a large group of proteins which recognize various pathogen-associated molecular patterns, are critical for the normal function of the innate immune system. Following their discovery many single nucleotide polymorphisms within TLRs and components of their signaling machinery have been discovered and subsequently implicated in a wide range of human diseases including atherosclerosis, sepsis, asthma, and immunodeficiency. This review discusses the effect of genetic variation on TLR function and how they may precipitate disease.Current Genomics 12/2012; 13(8):633-45. · 2.48 Impact Factor
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ABSTRACT: Innate immune mechanisms that follow early recognition of microbes influence the nature and magnitude of subsequent adaptive immune responses. Early detection of microbes depends on pattern recognition receptors that sense pathogen-associated molecular patterns or microbial-associated molecular patterns (PAMPS or MAMPs, respectively). The bacterial envelope contains MAMPs that include membrane proteins, lipopeptides, glycopolymers, and other pro-inflammatory molecules. Bacteria are selected by environmental pressures resulting in quantitative or qualitative changes in their envelope structures that often promote evasion of host immune responses and therefore, infection. However, recent studies have shown that slight, adaptive changes in MAMPs on the bacterial cell wall may result in their ability to induce the secretion not only of pro-inflammatory cytokines but also of anti-inflammatory cytokines. This effect can fine-tune the subsequent response to microbes expressing these MAMPs and lead to the establishment of a commensal state within the host rather than infectious disease. In this review, we will examine the plasticity of Toll-like receptor (TLR) 2 signaling as evidence of evolving MAMPs, using the better-characterized TLR4 as a template. We will review the role of differential dimerization of TLR2 and the arrangement of signaling complexes and co-receptors in determining the capacity of the host to recognize an array of TLR2 ligands and generate different immune responses to these ligands. Last, we will assess briefly how this plasticity may expand the array of interactions between microbes and immune systems beyond the traditional disease-causing paradigm.Frontiers in Immunology 01/2013; 4:347.
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ABSTRACT: Toll-like receptors trigger the innate immune response by activating various cell types such us macrophages and lymphocytes. We genotyped SNV of TLR3, TRL7, TLR8 and TLR10 in 863 Spanish and 150 Italian patients with Meniere's disease (MD) and 1,013 controls by using Taqman assays. Real-Time qPCR was used to measure the expression level of TLR10 in peripheral blood leukocytes. The overall dataset showed that the C allele and the CC genotype of rs11096955 in TLR10 gene were more commonly observed in controls than patients (corrected p = 1 × 10(-3), OR = 0.68 [95 % confidence interval, 0.54-0.84] for CC genotype; corrected p = 1.5 × 10(-5), OR = 0.75 [0.66-0.85] for allele C). Moreover, the CC genotype was more frequent in patients with uni- (19 %) than bilateral sensorineural hearing loss (SNHL) (13 %). Logistic regression demonstrated that the time since the onset of MD, Tumarkin crises, hearing stage and rs11096955 were independent factors influencing the risk of bilateral SNHL. In addition, rs11096955 influenced hearing loss progression in patients with bilateral MD. No change in expression of TLR10 was observed according to CC, CA or AA genotypes. Our data suggest that allelic variants of TLR10 gene may influence the susceptibility and time-course of hearing loss of MD in the European population.Immunogenetics 02/2013; · 2.89 Impact Factor