Circulating MicroRNAs in Patients with Active Pulmonary Tuberculosis

Abstract

Emerging evidence shows that microRNAs (miRNAs) play an important role in pathogen-host interactions. Circulating miRNAs have been repeatedly and stably detected in blood and hold promise to serve as molecular markers for diverse physiological and pathological conditions. To date, the relationship between circulating miRNAs and active pulmonary tuberculosis (TB) has not been reported. Using microarray-based expression profiling followed by real-time quantitative PCR validation, the levels of circulating miRNAs were compared between patients with active pulmonary tuberculosis and matched healthy controls. The receiver operating characteristic curve was used to evaluate the diagnostic effect of selected miRNA. Bioinformatic analysis was used to explore the potential roles of these circulating miRNAs in active pulmonary tuberculosis infection. Among 92 miRNAs significantly detected, 59 miRNAs were downregulated and 33 miRNAs were upregulated in the TB serum compared to their levels in the control serum. Interestingly, only two differentially expressed miRNAs were increased not only in the serum but also in the sputum of patients with active pulmonary tuberculosis compared to the levels for the healthy controls. Upregulated miR-29a could discriminate TB patients from healthy controls with reasonable sensitivity and specificity. A number of significantly enriched pathways regulated by these circulating miRNAs were predicted, and most of them were involved in acutephase response, inflammatory response, and the regulation of the cytoskeleton. In all, for the first time our results revealed that a number of miRNAs were differentially expressed during active pulmonary tuberculosis infection, and circulating miR-29a has great potential to serve as a marker for the detection of active pulmonary tuberculosis infection.

The mammalian microRNA response to bacterial infections

“…Along the same line, miR-29a was upregulated in both serum and sputum of patients with active pulmonary tuberculosis compared with the levels in healthy controls. 76 Opposite to the above observed induction of miR-29, it was shown that activated T cells of mice infected with M. bovis bacillus Calmette-Guerin (BCG) presented lower expression levels of miR-29 than the cells of their non-infected littermates. 73 This inhibition of miR-29 facilitated IFNγ production by the T cells and, accordingly, transgenic mice expressing a "sponge" designed to compete with endogenous miR-29 showed a greater resistance to infection with BCG or M. tuberculosis.…”

MicroRNA-223 controls susceptibility to tuberculosis by regulating lung neutrophil recruitment

“…Several studies suggest that key TBprotective cytokines, including TNF-α and IFN-γ, are regulated by miR-125b and miR-29, respectively (16,17). Moreover, screening approaches have tentatively pointed to miRNA signatures characteristic of active TB (18)(19)(20)(21)(22). Yet, no functional role in TB for any of these miRNAs has been elucidated, including the effects on chemokines and cell migration.…”

Dichotomous miR expression and immune responses following primary blood-stage malaria

“…They are recognized as important regulators of biological processes including T cell-and B cell-mediated immune responses and other immune functions (13,14). Studies of natural infection with influenza, Mycobacterium tuberculosis, and HIV have suggested that miR profiling studies can identify biomarkers of infection and predictors of clinical outcome (15)(16)(17)(18). However, the expression profile of host miRs during Plasmodium infection in humans has not yet been investigated and their ability to act as biomarkers for infection and/or immune control remains unknown.…”