MicroRNA let-7 Modulates the Immune Response to Mycobacterium tuberculosis Infection via Control of A20, an Inhibitor of the NF-κB Pathway.
2015 (English)In: Cell host & microbe, ISSN 1934-6069, Vol. 17, no 3, 345-56 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
elsevier , 2015. Vol. 17, no 3, 345-56 p.
Microbiology in the medical area
IdentifiersURN: urn:nbn:se:liu:diva-116362DOI: 10.1016/j.chom.2015.01.007ISI: 000350979800013PubMedID: 25683052OAI: oai:DiVA.org:liu-116362DiVA: diva2:798280