Dynamics of T-cell IFN-γ and miR-29a expression during active pulmonary tuberculosis

Awuah, Anthony Afum-Adjei; Ueberberg, Bianca; Owusu‐Dabo, Ellis; Frempong, Margaret; Jacobsen, Marc

doi:10.1093/intimm/dxu068

Cited by 26 publications

(19 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…With regard to M . tuberculosis studies, this miRNA has been identified as a serological biomarker [ 43 ] and was shown to be differentially expressed in leukocytes during TB infection [ 47 , 48 ]. MiR-29a has also been reported to be increased in human macrophages in response to M .…”

Section: Discussionmentioning

confidence: 99%

Analysis of Biobanked Serum from a Mycobacterium avium subsp paratuberculosis Bovine Infection Model Confirms the Remarkable Stability of Circulating miRNA Profiles and Defines a Bovine Serum miRNA Repertoire

et al. 2015

View full text Add to dashboard Cite

Johne’s Disease (JD) is a chronic enteritis of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). Current disease control strategies are hampered by the lack of sensitive and specific diagnostic modalities. Therefore, novel diagnostic and prognostic tools are needed, and circulating microRNAs (miRNAs) may hold potential in this area. The aims of this study were twofold: (i) to address the stability of miRNA in bovine sera from biobanked samples, and (ii) to assess the potential of miRNAs as biomarkers for JD disease progression. To address these aims we used bovine sera from an experimental MAP infection model that had been stored at -20°C for over a decade, allowing us to also assess the stability of miRNA profiles in biobanked serum samples through comparison with fresh sera. Approximately 100–200 intact miRNAs were identified in each sample with 83 of these being consistently detected across all 57 samples. The miRNA profile of the biobanked sera stored at -20°C for over 10 years was highly similar to the profile of <1 year-old sera stored at -80°C, with an overlap of 73 shared miRNAs. IsomiR analysis also indicated a distinct bovine serum-specific isomiR profile as compared to previously reported bovine macrophage miRNA profiles. To explore the prognostic potential of miRNA profiles cattle defined as seropositive for anti-MAP antibodies (n = 5) were compared against seronegative cattle (n = 7). No significant differential expressed miRNAs were detected at either the early (6 months) or late (43, 46 and 49 months) intervals (FDR≤0.05, fold-change≥1.5) across seropositive or seronegative animals. However, comparing pre-infection sera to the early and late time-points identified increased miR-29a and miR-92b abundance (2-fold) that may be due to blood-cell population changes over time (P<0.001). In conclusion our study has demonstrated that bovine circulating miRNAs retain their integrity under long-term sub-optimal storage temperatures opening the way for increased miRNA analyses from biobanked samples for a range of infectious and non-infectious diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Analysis of Biobanked Serum from a Mycobacterium avium subsp paratuberculosis Bovine Infection Model Confirms the Remarkable Stability of Circulating miRNA Profiles and Defines a Bovine Serum miRNA Repertoire

et al. 2015

View full text Add to dashboard Cite

show abstract

“…A subgroup of healthy contacts (n = 19) and tuberculosis patients (n = 32) was tested for M . tuberculosis PPD-specific immune response before and showed significant IFNγ expression [77]. We took heparinised blood (up to 30 ml) from each donor.…”

Section: Methodsmentioning

confidence: 99%

Aberrant plasma IL-7 and soluble IL-7 receptor levels indicate impaired T-cell response to IL-7 in human tuberculosis

et al. 2017

Self Cite

View full text Add to dashboard Cite

T-cell proliferation and generation of protective memory during chronic infections depend on Interleukin-7 (IL-7) availability and receptivity. Regulation of IL-7 receptor (IL-7R) expression and signalling are key for IL-7-modulated T-cell functions. Aberrant expression of soluble (s) and membrane-associated (m) IL-7R molecules is associated with development of autoimmunity and immune failure in acquired immune deficiency syndrome (AIDS) patients. Here we investigated the role of IL-7/IL-7R on T-cell immunity in human tuberculosis. We performed two independent case-control studies comparing tuberculosis patients and healthy contacts. This was combined with follow-up examinations for a subgroup of tuberculosis patients under therapy and recovery. Blood plasma and T cells were characterised for IL-7/sIL-7R and mIL-7R expression, respectively. IL-7-dependent T-cell functions were determined by analysing STAT5 phosphorylation, antigen-specific cytokine release and by analysing markers of T-cell exhaustion and inflammation. Tuberculosis patients had lower soluble IL-7R (p < 0.001) and higher IL-7 (p < 0.001) plasma concentrations as compared to healthy contacts. Both markers were largely independent and aberrant expression normalised during therapy and recovery. Furthermore, tuberculosis patients had lower levels of mIL-7R in T cells caused by post-transcriptional mechanisms. Functional in vitro tests indicated diminished IL-7-induced STAT5 phosphorylation and impaired IL-7-promoted cytokine release of Mycobacterium tuberculosis-specific CD4+ T cells from tuberculosis patients. Finally, we determined T-cell exhaustion markers PD-1 and SOCS3 and detected increased SOCS3 expression during therapy. Only moderate correlation of PD-1 and SOCS3 with IL-7 expression was observed. We conclude that diminished soluble IL-7R and increased IL-7 plasma concentrations, as well as decreased membrane-associated IL-7R expression in T cells, reflect impaired T-cell sensitivity to IL-7 in tuberculosis patients. These findings show similarities to pathognomonic features of impaired T-cell functions and immune failure described in AIDS patients.

show abstract

“…In contrast, another group reported decreased expression of miR-26a, miR-29a, and miR-142-3p in whole blood in children with tuberculosis compared to healthy children with latent Mtb infection (LTBI) 139 . However, Awuah et al concluded that although median miR-29a expression was slightly higher in TB patients, there was no significant difference compared with LTBI patients 140 . These plausible results might be due to choices of patients and starting material for miRNA quantification.…”

Section: Mirnas As Biomarkers For Bacterial Infectionmentioning

confidence: 97%

miRNAs reshape immunity and inflammatory responses in bacterial infection

Zhou

2018

Sig Transduct Target Ther

114

102

View full text Add to dashboard Cite

Pathogenic bacteria cause various infections worldwide, especially in immunocompromised and other susceptible individuals, and are also associated with high infant mortality rates in developing countries. MicroRNAs (miRNAs), small non-coding RNAs with evolutionarily conserved sequences, are expressed in various tissues and cells that play key part in various physiological and pathologic processes. Increasing evidence implies roles for miRNAs in bacterial infectious diseases by modulating inflammatory responses, cell penetration, tissue remodeling, and innate and adaptive immunity. This review highlights some recent intriguing findings, ranging from the correlation between aberrant expression of miRNAs with bacterial infection progression to their profound impact on host immune responses. Harnessing of dysregulated miRNAs in bacterial infection may be an approach to improving the diagnosis, prevention and therapy of infectious diseases.

show abstract

Dynamics of T-cell IFN-γ and miR-29a expression during active pulmonary tuberculosis

Cited by 26 publications

References 9 publications

Analysis of Biobanked Serum from a Mycobacterium avium subsp paratuberculosis Bovine Infection Model Confirms the Remarkable Stability of Circulating miRNA Profiles and Defines a Bovine Serum miRNA Repertoire

Analysis of Biobanked Serum from a Mycobacterium avium subsp paratuberculosis Bovine Infection Model Confirms the Remarkable Stability of Circulating miRNA Profiles and Defines a Bovine Serum miRNA Repertoire

Aberrant plasma IL-7 and soluble IL-7 receptor levels indicate impaired T-cell response to IL-7 in human tuberculosis

miRNAs reshape immunity and inflammatory responses in bacterial infection

Contact Info

Product

Resources

About