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Cell Host Microbe. 2015 Mar 11;17(3):345-356. doi: 10.1016/j.chom.2015.01.007. Epub 2015 Feb 12.

MicroRNA let-7 modulates the immune response to Mycobacterium tuberculosis infection via control of A20, an inhibitor of the NF-κB pathway.

Author information

1
Department of Chemistry, Bose Institute, Kolkata 700009, India.
2
Bioinformatics Centre, Bose Institute, Kolkata 700054, India.
3
Division of Molecular Medicine, Bose Institute, Kolkata 700054, India.
4
National Jalma Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra 282006, India.
5
Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden.
6
VIB Inflammation Research Center, Ghent University, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium.
7
Department of Chemistry, Bose Institute, Kolkata 700009, India. Electronic address: joyoti@vsnl.com.

Abstract

The outcome of the interaction between Mycobacterium tuberculosis (Mtb) and a macrophage depends on the interplay between host defense and bacterial immune subversion mechanisms. MicroRNAs critically regulate several host defense mechanisms, but their role in the Mtb-macrophage interplay remains unclear. MicroRNA profiling of Mtb-infected macrophages revealed the downregulation of miR-let-7f in a manner dependent on the Mtb secreted effector ESAT-6. We establish that let-7f targets A20, a feedback inhibitor of the NF-κB pathway. Expression of let-7f decreases and A20 increases with progression of Mtb infection in mice. Mtb survival is attenuated in A20-deficient macrophages, and the production of TNF, IL-1β, and nitrite, which are mediators of immunity to Mtb, is correspondingly increased. Further, let-7f overexpression diminishes Mtb survival and augments the production of cytokines including TNF and IL-1β. These results uncover a role for let-7f and its target A20 in regulating immune responses to Mtb and controlling bacterial burden.

PMID:
25683052
DOI:
10.1016/j.chom.2015.01.007
[Indexed for MEDLINE]
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