Dataset Information

Ex vivo mRNA expression of toll-like receptors during latent tuberculosis infection.

ABSTRACT:

Background

Understanding immune mechanisms, particularly the role of innate immune markers during latent TB infection remains elusive. The main objective of this study was to evaluate mRNA gene expression patterns of toll-like receptors (TLRs) as correlates of immunity during latent TB infection and further infer their roles as potential diagnostic biomarkers.

Methods

Messenger RNA (mRNA) levels were analysed in a total of 64 samples collected from apparently healthy children and adolescents latently infected with tuberculosis (n =?32) or non-infected (n =?32). Relative expression in peripheral blood of selected genes encoding TLRs (TLR-1, TLR-2, TLR-4, TLR-6 and TLR-9) was determined with a quantitative real-time polymerase chain reaction (qRT-PCR) using specific primers and florescent labelled probes and a comparative threshold cycle method to define fold change. Data were analysed using Graph-Pad Prism 7.01 for Windows and a p-value less than 0.05 was considered statistically significant.

Results

An increased mean fold change in the relative expression of TLR-2 and TLR-6 mRNA was observed in LTBI groups relative to non-LTBI groups (p ConclusionsAn increased mRNA expression of TLR-2 and TLR-6 was observed in latently infected individuals relative to those non-infected, possibly indicating the roles these biomarkers play in sustenance of the steady state interaction between the dormant TB bacilli and host immunity.

SUBMITTER: Alemnew B

PROVIDER: S-EPMC7842038 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Ex vivo mRNA expression of toll-like receptors during latent tuberculosis infection.

Alemnew Birhan B Hoff Soren T ST Abebe Tamrat T Abebe Markos M Aseffa Abraham A Howe Rawleigh R Wassie Liya L

BMC immunology 20210128 1

<h4>Background</h4>Understanding immune mechanisms, particularly the role of innate immune markers during latent TB infection remains elusive. The main objective of this study was to evaluate mRNA gene expression patterns of toll-like receptors (TLRs) as correlates of immunity during latent TB infection and further infer their roles as potential diagnostic biomarkers.<h4>Methods</h4>Messenger RNA (mRNA) levels were analysed in a total of 64 samples collected from apparently healthy children and ...[more]

PMID: 33509080

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Project description:BackgroundWe investigated whether polymorphisms in the toll-like receptor genes or gene-gene interactions are associated with susceptibility to latent tuberculosis infection (LTBI) or subsequent pulmonary tuberculosis (PTB) in a Chinese population.MethodsTwo matched case-control studies were undertaken. Previously reported polymorphisms in the toll-like receptors (TLRs) were compared between 422 healthy controls (HC) and 205 LTBI patients and between 205 LTBI patients and 109 PTB patients, to assess whether these polymorphisms and their interactions are associated with LTBI or PTB. A PCR-based restriction fragment length polymorphism analysis was used to detect genetic polymorphisms in the TLR genes. Nonparametric multifactor dimensionality reduction (MDR) was used to analyze the effects of interactions between complex disease genes and other genes or environmental factors.ResultsSixteen markers in TLR1, TLR2, TLR4, TLR6, TLR8, TLR9, and TIRAP were detected. In TLR2, the frequencies of the CC genotype (OR = 2.262; 95% CI: 1.433-3.570) and C allele (OR = 1.566; 95% CI: 1.223-1.900) in single-nucleotide polymorphism (SNP) rs3804100 were significantly higher in the LTBI group than in the HC group, whereas the GA genotype of SNP rs5743708 was associated with PTB (OR = 6.087; 95% CI: 1.687-21.968). The frequencies of the GG genotype of SNP rs7873784 in TLR4 (OR = 2.136; 95% CI: 1.312-3.478) and the CC genotype of rs3764879 in TLR8 (OR = 1.982; 95% CI: 1.292-3.042) were also significantly higher in the PTB group than in the HC group. The TC genotype frequency of SNP rs5743836 in TLR9 was significantly higher in the LTBI group than in the HC group (OR = 1.664; 95% CI: 1.201-2.306). An MDR analysis of gene-gene and gene-environment interactions identified three SNPs (rs10759932, rs7873784, and rs10759931) that predicted LTBI with 84% accuracy (p = 0.0004) and three SNPs (rs3804100, rs1898830, and rs10759931) that predicted PTB with 80% accuracy (p = 0.0001).ConclusionsOur results suggest that genetic variation in TLR2, 4, 8 and 9, implicating TLR-related pathways affecting the innate immunity response, modulate LTBI and PTB susceptibility in Chinese.

Project description:BackgroundIn Australia, demand for specialist infectious diseases services exceeds capacity to provide timely management of latent tuberculosis infection (LTBI) in areas of high refugee and asylum seeker settlement. A model for treating LTBI patients in primary care has been developed and piloted in a refugee-focused primary health service (Monash Health Refugee Health and Wellbeing [MHRHW]) and a universal primary care clinic. This study reports on the development and evaluation of the model, focusing on the model feasibility, and barriers and enablers to its success.MethodsA convergent mix-methods design was used to evaluate the model for treating LTBI patients in primary care, where a prospective cohort study of patients commencing treatment either at MHRHW or the universal primary care clinic determined the model feasibility, while focus groups with clinicians directly involved in treating these patients explored barriers and enablers to sustainability and success of the model.ResultsFrom January 2017 to April 2018, 65 patients with confirmed LTBI presented at participating clinics. Treatment was accepted by 31 (48%) patients, of whom 15(48%) were treated at MHRHW and 16 (52%) at the universal primary care clinic. The 6-months' treatment completion rate was higher at MHRHW compared to the universal primary care clinic (14 (93%) compared to 9 (56%) respectively, p = 0.0373). Reasons for non-completion included adverse reaction, opting out and relocation. At the completion of the pilot, 15 clinicians participated in two focus groups. Clinicians identified barriers and enablers for successful LTBI management at patient, provider, organisational and clinical levels. While barriers for treatment completion and adherence were consistent across the two pilot sites, enablers, such as resources to facilitate patient education and follow-up, were available only at MHRHW.ConclusionScreening and management of LTBI patients can be achieved within the primary care setting, considerate of barriers and enablers at patient, provider, organisational and clinical levels. Upscaling of a primary care response to the management of LTBI will require supporting primary care clinics with resources to employ dedicated clinical staff for patient education, follow-up communication and monitoring medication adherence.

Dataset Information

Ex vivo mRNA expression of toll-like receptors during latent tuberculosis infection.

Background

Methods

Results

Publications

Ex vivo mRNA expression of toll-like receptors during latent tuberculosis infection.

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