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Human Genomics of Mycobacterium tuberculosis Infection and Disease.

ABSTRACT: Purpose of review:The study of the genetic basis of tuberculosis pathogenesis has benefited from powerful technological innovations, a more structured definition of latent and clinical manifestations of the disease, and the application of functional genomics approaches. This short review aims to summarize recent advances and to provide a link with results of previous human genetic studies of tuberculosis susceptibility. Recent findings:Transcriptomics has been shown to be a useful tool to predict progression from latency to clinical disease while functional genomics has traced the molecular events that link pathogen-triggered gene expression and host genetics. Resistance to infection with Mycobacterium tuberculosis has been revealed to be strongly impacted by host genetics. Host genomics of clinical disease has been shown to be most powerful when focusing on carefully selected clinical entities and possibly by considering host pathogen combinations. Summary:Future studies need to build on the latest molecular findings to define disease subtypes to successfully elucidate the human genetic component in tuberculosis pathogenesis.

SUBMITTER: Orlova M

PROVIDER: S-EPMC5703416 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Human Genomics of <i>Mycobacterium tuberculosis</i> Infection and Disease.

Orlova Marianna M Schurr Erwin E

Current genetic medicine reports 20170725 3

<h4>Purpose of review</h4>The study of the genetic basis of tuberculosis pathogenesis has benefited from powerful technological innovations, a more structured definition of latent and clinical manifestations of the disease, and the application of functional genomics approaches. This short review aims to summarize recent advances and to provide a link with results of previous human genetic studies of tuberculosis susceptibility.<h4>Recent findings</h4>Transcriptomics has been shown to be a useful ...[more]

PMID: 29201558

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Project description:BackgroundLatent tuberculosis infection (LTBI) relies on a homeostasis of macrophages and Mycobacterium tuberculosis (Mtb). The small heat shock protein, Mtb Hsp16.3 (also known as latency-associated antigen), plays an important role in Mtb persistence within macrophages. However, the mechanism of LTBI remains elusive. The aim of this study was to delineate LTBI-related miRNA expression in U937 macrophages expressing Mtb Hsp16.3 protein. U937 macrophages were infected with an integrase-deficient Lentivirus vector to transiently express Mtb Hsp16.3, and green fluorescent protein (GFP) as a control. We used a microRNA (miRNA) microarray chip containing more than 1000 probes to identify the significant differentially expressed miRNAs in the infected U937 cells, and employed real-time quantitative polymerase chain reaction (qRT-PCR) for validation. Furthermore, we confirmed these candidate LTBI-related miRNAs in peripheral blood mononuclear cells from subjects with LTBI and in healthy control individuals. Functional annotation prediction of miRNA target genes and pathway enrichment analyses were used to explore the putative links between these miRNAs and LTBI.ResultsAnalysis of the miRNA expression profile identified 149 miRNAs that were differentially expressed in U937 macrophages expressing Mtb Hsp16.3 compared with the control expressing GFP. The expression level of seven miRNAs (miR-424-5p, miR-493-5p, miR-296-5p, miR-27b-3p, miR-377-5p, miR-3680-5p, miR-191-5p) were validated by qRT-PCR. The expression level of four miRNAs (miR-424-5p, miR-27b-3p, miR-377-5p, miR-3680-5p) in the peripheral blood mononuclear cells samples from LTBI and healthy participants reflected the altered patterns observed in the microarray profile. The bioinformatic analyses suggest that the miRNAs may regulate Mtb latent infection by affecting the development of macrophage cells.ConclusionsThe results suggest that miRNA expression may play a considerable role in the pathogenesis of LTBI, and this would increase our understanding of the molecular basis of Hsp16.3-facilitated Mtb survival in macrophages.

Dataset Information

Human Genomics of Mycobacterium tuberculosis Infection and Disease.

Publications

Human Genomics of <i>Mycobacterium tuberculosis</i> Infection and Disease.

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