Abstract
Tuberculosis (TB), which is a frequent and important infectious disease caused by Mycobacterium tuberculosis, has resulted in an extremely high burden of morbidity and mortality. The importance of intestinal dysbacteriosis in regulating host immunity has been implicated in TB, and accumulating evidence suggests that microRNAs (miRNAs) might act as a key mediator in maintaining intestinal homeostasis through signaling networks. However, the involvement of miRNA in gut microbiota, TB and the host immune system remains unknown. Here we showed that intestinal dysbacteriosis increases the susceptibility to TB and remotely increased the expression of miR-21 in lung. Systemic antagonism of miR-21 enhanced IFN-γ production and further conferred immune protection against TB. Molecular experiments further indicated that miR-21a-3p could specifically target IFN-γ mRNA. These findings revealed regulatory pathways implicating intestinal dysbacteriosis induced-susceptibility to TB: intestinal dysbiosis→lung miRNA→targeting IFN-γ→impaired anti-TB immunity. This study also suggested that deregulated miRNAs by commensal bacteria could become promising targets as TB therapeutics.
Highlights
Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis (TB), infects onethird of the world population and leads to high morbidity and mortality (Dickson et al, 2016)
We hypothesized that microbiome dysbiosis would have a profound impact on the microbiota that alters the nutritional landscape of the gut or the lung and increase the host susceptibility to TB due to aberrant immune response (Modi et al, 2014; Zanvit et al, 2015)
To evaluate the role of antibiotics on the development of TB infection, we further investigated whether antibiotics would directly affect lung pathology by hematoxylin and eosin (H&E) staining of lung sections without M.tuberculosis infection
Summary
Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis (TB), infects onethird of the world population and leads to high morbidity and mortality (Dickson et al, 2016). Clinical options available to combat TB include chemotherapeutic agents and the preventative vaccine Mycobacterium Bovis bacillus Calmette–Guérin (BCG) which has been undermined due to the broad emergence of drug-resistant strains of M. tuberculosis (Dheda et al, 2014), insufficient protection of BCG efficacy against pulmonary TB in adolescents and adults (Colditz et al, 1994) as well as HIV-1 co-infection. Accumulating evidence indicates that gut microbiota dysbiosis provokes susceptibility to infectious diseases. It advocates the importance of commensal bacteria to host health as commensal microbes can calibrate innate and adaptive immune responses and impact the activation threshold for pathogenic stimulations (Ivanov and Honda, 2012). Treatment with broad-spectrum antibiotics decreased TNFα and IFN-γ production by CD8 + T cells and compromised anti-viral immunity during influenza infection (Abt et al, 2012)
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