Abstract
The emerging roles of microRNAs (miRNAs) and pulmonary epithelial cells in regulating the immune response against microbial invasion has attracted increasing attention in recent years, however, the immunoregulatory roles of miRNAs in the pulmonary epithelial cells in response to mycobacterial infection has not been fully demonstrated. In this study, we show that miR-124 expression is induced upon Mycobacterium bovis Bacillus Calmette-Guerin (BCG) infection in A549 alveolar epithelial cells and murine lungs. miR-124 is able to modulate Toll-like receptor (TLR) signaling in A459 cells. In this regard, multiple components, including TLR6, myeloid differentiation factor 88 (MyD88), TNFR-associated factor 6 and tumor necrosis factor-α of the TLR signaling cascade are directly regulated by miR-124 in response to BCG stimulation. In addition, miR-124 expression was induced upon MyD88 overexpression and/or BCG stimulation, while silencing MyD88 expression by small interfering RNA dramatically down-regulated miR-124 transcription in A549 cells. These results indicate an underlying negative feedback mechanism between miR-124 and MyD88 in alveolar epithelial cells to prevent an excessive inflammatory response during mycobacterial infection. These observations suggest that miR-124 is a potential target for preventive and therapeutic intervention against the pulmonary tuberculosis, an infectious disease caused by Mycobacterium tuberculosis infection.
Highlights
Each year, an estimated nine million people contract human tuberculosis (TB), and two million people die from the disease worldwide [1]
In order to investigate the role of miR-124 in alveolar epithelial cells in response to mycobacterial infection, miR-124 transcripts were evaluated in A549 cells and murine lungs following Bacillus Calmette-Guerin (BCG)
We investigated the function of miR-124 in A549 alveolar epithelial cells in response to BCG infection
Summary
An estimated nine million people contract human tuberculosis (TB), and two million people die from the disease worldwide [1]. Mycobacterium tuberculosis bacillus (Mtb) is the causative agent of TB. Mtb undergoes various genomic reprogramming events upon infection, which subsequently prevent the immune system from completely eliminating latent infectious agents [2]. Despite the identification of cell-mediated immune responses and pro-inflammatory cytokines and chemokines that play crucial roles against Mtb infection, the underlying mechanism controlling Mtb adaptation remains poorly understood [3]. Mtb primarily targets the pulmonary macrophages, and pervious studies on immune responses against Mtb infection have focused mainly on the alveolar macrophages or dendritic cells (DCs) [4,5]. Increasing evidence has suggested that pulmonary epithelial cells—to which Mtb is able to directly bind and penetrate— represent an important step in the Mtb infection process [6,7,8]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
