title: MicroRNA let-7 modulates the immune response to Mycobacterium tuberculosis infection via control of A20, an inhibitor of the NF-κB pathway.
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.
authors: Department of Chemistry, Bose Institute, Kolkata 700009, India.
authors: Manish
authors: M
authors: Kumar
authors: Department of Chemistry, Bose Institute, Kolkata 700009, India.
authors: Sanjaya Kumar
authors: SK
authors: Sahu
authors: Department of Chemistry, Bose Institute, Kolkata 700009, India.
authors: Ranjeet
authors: R
authors: Kumar
authors: Department of Chemistry, Bose Institute, Kolkata 700009, India.
authors: Arijita
authors: A
authors: Subuddhi
authors: Bioinformatics Centre, Bose Institute, Kolkata 700054, India.
authors: Ranjan Kumar
authors: RK
authors: Maji
authors: Division of Molecular Medicine, Bose Institute, Kolkata 700054, India.
authors: Kuladip
authors: K
authors: Jana
authors: National Jalma Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra 282006, India.
authors: Pushpa
authors: P
authors: Gupta
authors: Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden.
authors: Johanna
authors: J
authors: Raffetseder
authors: Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden.
authors: Maria
authors: M
authors: Lerm
authors: Bioinformatics Centre, Bose Institute, Kolkata 700054, India.
authors: Zhumur
authors: Z
authors: Ghosh
authors: VIB Inflammation Research Center, Ghent University, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium.
authors: Geert
authors: G
authors: van Loo
authors: VIB Inflammation Research Center, Ghent University, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium.
authors: Rudi
authors: R
authors: Beyaert
authors: National Jalma Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra 282006, India.
authors: Umesh D
authors: UD
authors: Gupta
authors: Department of Chemistry, Bose Institute, Kolkata 700009, India.
authors: Manikuntala
authors: M
authors: Kundu
authors: Department of Chemistry, Bose Institute, Kolkata 700009, India. Electronic address: joyoti@vsnl.com.
authors: Joyoti
authors: J
authors: Basu
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors*; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D017422:Sequence Analysis, DNA; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs; D016328:NF-kappa B; D009687:Nuclear Proteins; C487931:mirnlet7 microRNA, human; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3