title: The microRNA miR-29 controls innate and adaptive immune responses to intracellular bacterial infection by targeting interferon-γ.
abstract: Interferon-γ (IFN-γ) has a critical role in immune responses to intracellular bacterial infection. MicroRNAs (miRNAs) are important in the regulation of innate and adaptive immunity. However, whether miRNAs can directly target IFN-γ and regulate IFN-γ production post-transcriptionally remains unknown. Here we show that infection of mice with Listeria monocytogenes or Mycobacterium bovis bacillus Calmette-Guérin (BCG) downregulated miR-29 expression in IFN-γ-producing natural killer cells, CD4(+) T cells and CD8(+) T cells. Moreover, miR-29 suppressed IFN-γ production by directly targeting IFN-γ mRNA. We developed mice with transgenic expression of a 'sponge' target to compete with endogenous miR-29 targets (GS29 mice). We found higher serum concentrations of IFN-γ and lower L. monocytogenes burdens in L. monocytogenes-infected GS29 mice than in their littermates. GS29 mice had enhanced T helper type 1 (T(H)1) responses and greater resistance to infection with BCG or Mycobacterium tuberculosis. Therefore, miR-29 suppresses immune responses to intracellular pathogens by targeting IFN-γ.
authors.affiliation: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Ma
authors.forename: Sheng
authors.initials: S
authors.lastname: Xu
authors.forename: Xingguang
authors.initials: X
authors.lastname: Liu
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xiongfei
authors.initials: X
authors.lastname: Xu
authors.forename: Mofang
authors.initials: M
authors.lastname: Liu
authors.forename: Minmin
authors.initials: M
authors.lastname: Hua
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Hangping
authors.initials: H
authors.lastname: Yao
authors.forename: Xuetao
authors.initials: X
authors.lastname: Cao
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics / Q000276:immunology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002417:Cattle; D015169:Colony Count, Microbial; D020868:Gene Silencing; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D016086:Lentivirus; D008089:Listeria monocytogenes / Q000254:growth & development; D008088:Listeriosis / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D009163:Mycobacterium bovis / Q000254:growth & development; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000037:antagonists & inhibitors* / Q000378:metabolism; D058408:Th1-Th2 Balance; D014162:Transfection; D014380:Tuberculosis, Bovine / Q000276:immunology / Q000382:microbiology
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D007371:Interferon-gamma