Mycobacterium bovis BCG triggered MyD88 induces miR-124 feedback negatively regulates immune response in alveolar epithelial cells.
The emerging roles of microRNAs (miRNAs) and pulmonary epithelial cells in regulating the immune response against microbial invasion has attracted increasing attention in recent years, however, the immunoregulatory roles of miRNAs in the pulmonary epithelial cells in response to mycobacterial infection has not been fully demonstrated. In this study, we show that miR-124 expression is induced upon Mycobacterium bovis Bacillus Calmette-Guerin (BCG) infection in A549 alveolar epithelial cells and murine lungs. miR-124 is able to modulate Toll-like receptor (TLR) signaling in A459 cells. In this regard, multiple components, including TLR6, myeloid differentiation factor 88 (MyD88), TNFR-associated factor 6 and tumor necrosis factor-α of the TLR signaling cascade are directly regulated by miR-124 in response to BCG stimulation. In addition, miR-124 expression was induced upon MyD88 overexpression and/or BCG stimulation, while silencing MyD88 expression by small interfering RNA dramatically down-regulated miR-124 transcription in A549 cells. These results indicate an underlying negative feedback mechanism between miR-124 and MyD88 in alveolar epithelial cells to prevent an excessive inflammatory response during mycobacterial infection. These observations suggest that miR-124 is a potential target for preventive and therapeutic intervention against the pulmonary tuberculosis, an infectious disease caused by Mycobacterium tuberculosis infection.
Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, Yinchuan, Ningxia, China; College of Life Science, Ningxia University, Yinchuan, Ningxia, China.
Chunyan
C
Ma
Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, Yinchuan, Ningxia, China; College of Life Science, Ningxia University, Yinchuan, Ningxia, China.
Yong
Y
Li
Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, Yinchuan, Ningxia, China; College of Life Science, Ningxia University, Yinchuan, Ningxia, China.
Jin
J
Zeng
Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, Yinchuan, Ningxia, China; College of Life Science, Ningxia University, Yinchuan, Ningxia, China.
Xiaoling
X
Wu
Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, Yinchuan, Ningxia, China; College of Life Science, Ningxia University, Yinchuan, Ningxia, China.
Xiaoming
X
Liu
Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, Yinchuan, Ningxia, China; College of Life Science, Ningxia University, Yinchuan, Ningxia, China.
Yujiong
Y
Wang
D056704:Adaptive Immunity / Q000235:genetics*; D000818:Animals; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D025461:Feedback, Physiological; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D009164:Mycobacterium Infections / Q000235:genetics / Q000276:immunology; D009163:Mycobacterium bovis / Q000502:physiology*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D020545:Respiratory Mucosa / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology
D035683:MicroRNAs; C540079:Mirn124 microRNA, mouse; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88