Can the battle against tuberculosis gain from epigenetic research?

Esterhuyse, Maria M.; Linhart, Heinz; Kaufmann, Stefan H. E.

doi:10.1016/j.tim.2012.03.002

Cited by 31 publications

(16 citation statements)

References 74 publications

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“…These findings suggest that NATs may play a significant role in regulating the host macrophage response following infection with pathogenic agents, including mycobacteria [52,65]. …”

Section: Discussionmentioning

confidence: 99%

Whole-transcriptome, high-throughput RNA sequence analysis of the bovine macrophage response to Mycobacterium bovis infection in vitro

et al. 2013

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BackgroundMycobacterium bovis, the causative agent of bovine tuberculosis, is an intracellular pathogen that can persist inside host macrophages during infection via a diverse range of mechanisms that subvert the host immune response. In the current study, we have analysed and compared the transcriptomes of M. bovis-infected monocyte-derived macrophages (MDM) purified from six Holstein-Friesian females with the transcriptomes of non-infected control MDM from the same animals over a 24 h period using strand-specific RNA sequencing (RNA-seq). In addition, we compare gene expression profiles generated using RNA-seq with those previously generated by us using the high-density Affymetrix® GeneChip® Bovine Genome Array platform from the same MDM-extracted RNA.ResultsA mean of 7.2 million reads from each MDM sample mapped uniquely and unambiguously to single Bos taurus reference genome locations. Analysis of these mapped reads showed 2,584 genes (1,392 upregulated; 1,192 downregulated) and 757 putative natural antisense transcripts (558 upregulated; 119 downregulated) that were differentially expressed based on sense and antisense strand data, respectively (adjusted P-value ≤ 0.05). Of the differentially expressed genes, 694 were common to both the sense and antisense data sets, with the direction of expression (i.e. up- or downregulation) positively correlated for 693 genes and negatively correlated for the remaining gene. Gene ontology analysis of the differentially expressed genes revealed an enrichment of immune, apoptotic and cell signalling genes. Notably, the number of differentially expressed genes identified from RNA-seq sense strand analysis was greater than the number of differentially expressed genes detected from microarray analysis (2,584 genes versus 2,015 genes). Furthermore, our data reveal a greater dynamic range in the detection and quantification of gene transcripts for RNA-seq compared to microarray technology.ConclusionsThis study highlights the value of RNA-seq in identifying novel immunomodulatory mechanisms that underlie host-mycobacterial pathogen interactions during infection, including possible complex post-transcriptional regulation of host gene expression involving antisense RNA.

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“…These findings suggest that NATs may play a significant role in regulating the host macrophage response following infection with pathogenic agents, including mycobacteria [52,65]. …”

Section: Discussionmentioning

confidence: 99%

Whole-transcriptome, high-throughput RNA sequence analysis of the bovine macrophage response to Mycobacterium bovis infection in vitro

et al. 2013

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“…Genetic [98] and epigenetic [99] mechanisms are likely to contribute to treatment response through numerous pathways such as plasticity of the immune response and pharmacogenomic variability. As demonstrated by Prideaux et al , differential spatial distribution and kinetics of accumulation in diseased tissue can help predict sterilizing activity of existing and new drugs [100].…”

Section: Five Year Viewmentioning

confidence: 99%

Assessment of treatment response in tuberculosis

Rockwood

Bruyn

Morris

et al. 2016

Expert Review of Respiratory Medicine

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Antibiotic treatment of tuberculosis has a duration of several months. There is significant variability of the host immune response and the pharmacokineticpharmacodynamic properties of Mycobacterium tuberculosis sub-populations at the site of disease. A limitation of sputum-based measures of treatment response may be sub-optimal detection and monitoring of Mycobacterium tuberculosis sub-populations. Potential biomarkers and surrogate endpoints should be benchmarked against hard clinical outcomes (failure/relapse/death) and may need tailoring to specific patient populations. Here, we assess the evidence supporting currently utilized and future potential host and pathogen-based models and biomarkers for monitoring treatment response in active and latent tuberculosis. Biomarkers for monitoring treatment response in extrapulmonary, pediatric and drug resistant tuberculosis are research priorities.

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“…It is also possible that somatic mutations and epigenetic effects have a substantial impact on clinical susceptibility to TB, particularly in patients with late-onset disease [70]. Epigenetic mechanisms play a critical role in the immune system [109], and their investigation, particularly through GW analyses of the methylome [110,111], should provide new insight into the genetic basis of infection and clinical TB [112]. These epigenetic factors may be influenced by environmental and/or other host factors, such as diet, vitamin status or ageing [113,114], leading to additional possible gene × environment interaction effects.…”

Section: Perspectivesmentioning

confidence: 99%

Human genetics of tuberculosis: a long and winding road

Abel

El-Baghdadi

Bousfiha

et al. 2014

Phil. Trans. R. Soc. B

162

144

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Only a small fraction of individuals exposed to Mycobacterium tuberculosis develop clinical tuberculosis (TB). Over the past century, epidemiological studies have shown that human genetic factors contribute significantly to this interindividual variability, and molecular progress has been made over the past decade for at least two of the three key TB-related phenotypes: (i) a major locus controlling resistance to infection with M. tuberculosis has been identified, and (ii) proof of principle that severe TB of childhood can result from single-gene inborn errors of interferon-γ immunity has been provided; genetic association studies with pulmonary TB in adulthood have met with more limited success. Future genetic studies of these three phenotypes could consider subgroups of subjects defined on the basis of individual (e.g. age at TB onset) or environmental (e.g. pathogen strain) factors. Progress may also be facilitated by further methodological advances in human genetics. Identification of the human genetic variants controlling the various stages and forms of TB is critical for understanding TB pathogenesis. These findings should have major implications for TB control, in the definition of improved prevention strategies, the optimization of vaccines and clinical trials and the development of novel treatments aiming to restore deficient immune responses.

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Can the battle against tuberculosis gain from epigenetic research?

Cited by 31 publications

References 74 publications

Whole-transcriptome, high-throughput RNA sequence analysis of the bovine macrophage response to Mycobacterium bovis infection in vitro

Whole-transcriptome, high-throughput RNA sequence analysis of the bovine macrophage response to Mycobacterium bovis infection in vitro

Assessment of treatment response in tuberculosis

Human genetics of tuberculosis: a long and winding road

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