title: microRNA-124 negatively regulates TLR signaling in alveolar macrophages in response to mycobacterial infection.
abstract: The emerging roles of microRNAs (miRNAs) in regulating immune responses have attracted increasing attention in recent years; and the alveolar macrophages (AMs) are the main targets of mycobacterial infection, which play a pivotal role in the pathogenesis of Mycobacterium tuberculosis infection. However, the immunoregulatory role of miRNAs in AMs has not been fully demonstrated. In this study, we find that miR-124 is up-regulated in the peripheral leukocytes of patients with pulmonary tuberculosis; furthermore, the expression miR-124 can be induced upon Mycobacterium bovis Bacillus Calmette-Guerin (BCG) infection in both RAW264.7 AM cells in vitro and murine AMs in vivo. Mechanistically, miR-124 is able to modulate toll-like receptor (TLR) signaling activity in RAW264.7 cells in response to BCG infection. In this regard, multiple components of TLR signaling cascade, including the TLR6, myeloid differentiation factor 88 (MyD88), TNFR-associated factor 6 and tumor necrosis factor-α are directly targeted by miR-124. In addition, both overexpression of TLR signaling adaptor MyD88 and BCG infection are able to augment miR-124 transcription, while MyD88 expression silenced by small interfering RNA dramatically suppresses miR-124 expression in AMs in vitro. Moreover, the abundance of miR-124 transcript in murine AMs of MyD88 deficient mice is significantly less than that of their wild-type or heterozygous littermates; and the BCG infection fails to induce miR-124 expression in the lung of MyD88 deficient mouse. These results indicate a negative regulatory role of miR-124 in fine-tuning inflammatory response in AMs upon mycobacterial infection, in part through a mechanism by directly targeting TLR signaling.
authors.affiliation: Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China and College of Life Science, Ningxia University, Yinchuan 750021, Ningxia, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Ma
authors.affiliation: Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China and College of Life Science, Ningxia University, Yinchuan 750021, Ningxia, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China and College of Life Science, Ningxia University, Yinchuan 750021, Ningxia, China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China and College of Life Science, Ningxia University, Yinchuan 750021, Ningxia, China.
authors.forename: Guangcun
authors.initials: G
authors.lastname: Deng
authors.affiliation: Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China and College of Life Science, Ningxia University, Yinchuan 750021, Ningxia, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Wu
authors.affiliation: Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China and College of Life Science, Ningxia University, Yinchuan 750021, Ningxia, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China and College of Life Science, Ningxia University, Yinchuan 750021, Ningxia, China.
authors.forename: Xiujing
authors.initials: X
authors.lastname: Hao
authors.affiliation: Tuberculosis Hospital of Ningxia, Yinchuan 750021, Ningxia, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Wang
authors.affiliation: Tuberculosis Hospital of Ningxia, Yinchuan 750021, Ningxia, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong SAR, China.
authors.forename: William C S
authors.initials: WC
authors.lastname: Cho
authors.affiliation: Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China and College of Life Science, Ningxia University, Yinchuan 750021, Ningxia, China. Electronic address: erc1080@gmail.com.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China and College of Life Science, Ningxia University, Yinchuan 750021, Ningxia, China. Electronic address: wyj@nxu.edu.cn.
authors.forename: Yujiong
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D009163:Mycobacterium bovis / Q000276:immunology; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D051193:Toll-Like Receptors / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000235:genetics / Q000276:immunology*; D055815:Young Adult
chemical_list: C509207:MIRN124 microRNA, human; D035683:MicroRNAs; D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors
keywords: Alveolar macrophage; Inflammatory response; Mycobacterial infection; Toll-like receptor; microRNA-124