Mycobacterium marinum down-regulates miR-148a in macrophages in an EsxA-dependent manner.

Affiliation

Department of Biological Sciences, Border Biomedical Research Center, University of Texas at El Paso, 500 West University Avenue, El Paso, TX 79968, USA. Electronic address: [Email]

Abstract

As a key virulence factor of Mycobacterium tuberculosis, EsxA is not only involved in phagosome rupture, but also functions in stimulation of immune responses in macrophages. Here, we report thatmiR-148a is down-regulated in the macrophages infected with Mycobacterium marinum (Mm). Using the knockout strain Mm∆EsxA/B, recombinant EsxA, EsxB and EsxA/B heterodimer proteins, we provide evidence that down-regulation of miR-148ais dependent on EsxA, and up-regulation of miR-148a reduces Mm intracellular survival. Moreover, up-regulation of miR-148a down-regulates the pro-inflammatory cytokines (e.g. TNF-α and IL-1β) and the TLR4-mediated NF-κB activation. Together, miR-148a may function as an anti-inflammation modulator in responses to mycobacterial infection. Regulation of miR-148a may provide a novel venue in development of therapies in tuberculosis.

Keywords

ESAT-6,EsxA,Macrophages,Mycobacterium tuberculosis,miR-148a,