Utility of mycobacterium tuberculosis Rv0081-specific host gene expression to distinguish latent infection from active tuberculosis disease

ABSTRACT Commensal microbial communities have immense effects on their vertebrate hosts, contributing to a number of physiological functions, as well as host fitness. In particular, host immunity is strongly linked to microbiota composition through poorly understood bi-directional links. Gene expression may be a potential mediator of these links between microbial communities and host function. However, few studies have investigated connections between microbiota composition and expression of host immune genes in complex systems. Here, we leverage a large study of laboratory-raised fish from the species Gasterosteus aculeatus (three-spined stickleback) to document correlations between gene expression and microbiome composition. First, we examined correlations between microbiome alpha diversity and gene expression. Our results demonstrate robust positive associations between microbial alpha diversity and expression of host immune genes. Next, we examined correlations between host gene expression and abundance of microbial taxa. We identified 15 microbial families that were highly correlated with host gene expression. These families were all tightly correlated with host expression of immune genes and processes, falling into one of three categories—those positively correlated, negatively correlated, and neutrally related to immune processes. Furthermore, we highlight several important immune processes that are commonly associated with the abundance of these taxa, including both macrophage and B cell functions. Further functional characterization of microbial taxa will help disentangle the mechanisms of the correlations described here. In sum, our study supports prevailing hypotheses of intimate links between host immunity and gut microbiome composition. IMPORTANCE Here, we document associations between host gene expression and gut microbiome composition in a nonmammalian vertebrate species. We highlight associations between expression of immune genes and both microbiome diversity and abundance of specific microbial taxa. These findings support other findings from model systems which have suggested that gut microbiome composition and host immunity are intimately linked. Furthermore, we demonstrate that these correlations are truly systemic; the gene expression detailed here was collected from an important fish immune organ (the head kidney) that is anatomically distant from the gut. This emphasizes the systemic impact of connections between gut microbiota and host immune function. Our work is a significant advancement in the understanding of immune-microbiome links in nonmodel, natural systems.

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Microbiota Modulates Host Gene Expression via MicroRNAs

Gastroenterology ◽

10.1016/s0016-5085(11)62754-6 ◽

2011 ◽

Vol 140 (5) ◽

pp. S-663 ◽

Cited By ~ 2

Author(s):

Guillaume Dalmasso ◽

Hang Thi Thu Nguyen ◽

Yutao Yan ◽

Hamed Laroui ◽

Moiz A. Charania ◽

...

Keyword(s):

Gene Expression ◽

Host Gene ◽

Host Gene Expression

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Abstract 19222: Hypoxia Regulated Circular RNAs Control Endothelial Cell Functions (Best of Basic Science Abstract)

Circulation ◽

10.1161/circ.132.suppl_3.19222 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Andreas W Heumüller ◽

Jes-Niels Boeckel ◽

Nicolas Jaé ◽

Yuliya Ponomareva ◽

Wei Chen ◽

...

Keyword(s):

Gene Expression ◽

Endothelial Cells ◽

Network Formation ◽

Rare Event ◽

Expression Regulation ◽

Host Gene ◽

Circular Rnas ◽

Host Gene Expression ◽

Go Annotation ◽

Cell Functions

Circular RNAs (circRNAs) are non-coding RNAs generated by back-splicing. Back-splicing has been considered as a rare event, but circRNAs were recently found to be abundantly expressed among a variety of human cells and tissues. Nevertheless, the expressional regulation, processing and biological functions of circRNAs are largely unknown. Cytoplasmic circRNAs can bind and trap microRNAs, whereas nuclear circRNAs may affect host gene expression. However, the expression, regulation and functions of circRNAs in endothelial cells have not been determined so far. In this study, basal expression and regulation of circRNAs by hypoxia in human umbilical endothelial cells (HUVEC) were analyzed using deep sequencing. Among the identified 7,388 circRNAs, 2,875 had not been annotated before. We further validated the expression of 40 selected circRNAs by RT-PCR and found that the majority is resistant to RNase R digestion, lacks polyadenylation and is localized to the cytoplasm. Cloning and subsequent sequencing validated the newly generated back splice sites for selected circRNAs. Furthermore, analysis of RNA-seq data revealed that circRNAs, particularly the cytoplasmatic circular RNA cZNF292, are significantly regulated by hypoxia in HUVECs. The siRNA-mediated knockdown of HIF-1α had no effect on cZNF292 induction under hypoxia, suggesting a HIF-1α independent regulation. Most importantly, siRNA-mediated knockdown of cZNF292 significantly reduced spheroid sprouting and network formation of endothelial cells. Furthermore, knockdown of cZNF292 had no effect on its host gene expression. Exon array analysis after cZNF292 knockdown revealed a significant expressional upregulation of 167 as well as a significant expressional downregulation of 123 genes of which most were associated with metabolic processes according to GO annotation. Analysis of Ago-HITS-CLIP data revealed no putative miR-binding sites, suggesting that cZNF292 does not act as a miR-sponge. Taken together, we show for the first time the expression, regulation and function of circRNAs in endothelial cells. The circRNA cZNF292 is regulated by hypoxia and has an important angiogenic function in endothelial cells.

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Active Pulmonary Tuberculosis Triggered by Interferon Beta-1b Therapy of Multiple Sclerosis: Four Case Reports and a Literature Review

Medicina ◽

10.3390/medicina56040202 ◽

2020 ◽

Vol 56 (4) ◽

pp. 202 ◽

Cited By ~ 2

Author(s):

Carmen Adella Sirbu ◽

Elena Dantes ◽

Cristina Florentina Plesa ◽

Any Docu Axelerad ◽

Minerva Claudia Ghinescu

Keyword(s):

Multiple Sclerosis ◽

Mycobacterium Tuberculosis ◽

Literature Review ◽

Interferon Beta ◽

Latent Infection ◽

Case Reports ◽

Active Tuberculosis ◽

Active Pulmonary Tuberculosis ◽

Disease Modifying Therapies ◽

Disease Modifying

In this paper, we reported on four cases of severe pulmonary active tuberculosis in patients with multiple sclerosis (MS) undergoing interferon beta-1b (IFNβ-1b) therapy. Disease-modifying therapies (DMTs) in MS may increase the risk of developing active tuberculosis (TB) due to their impact on cellular immunity. Screening for latent infection with Mycobacterium tuberculosis (LTBI) should be performed, not only for the newer DMTs (alemtuzumab, ocrelizumab) but also for IFNβ-1b, alongside better supervision of these patients.

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