MiR-381-3p Regulates the Antigen-Presenting Capability of Dendritic Cells and Represses Antituberculosis Cellular Immune Responses by Targeting CD1c.
Tuberculosis is still the widest spread infectious disease in the world, and more in-depth studies are needed on the interaction between the pathogen and the host. Due to the highest lipid components in Mycobacterium tuberculosis, the CD1 family that specifically presents antigenic lipids plays important roles in the antituberculosis immunity, especially CD1c, which functions as the intracellular Ag inspector at the full intracellular range. However, downregulation of the CD1c mRNA level has been observed in M. tuberculosis-infected cells, which is consistent with the regulatory mechanism of miRNA on gene expression. In this study, through combinatory analysis of previous miRNA transcriptomic assays and bioinformatic predictions by web-based algorithms, miR-381-3p was predicted to bind the 3'-untranslated region of CD1c gene. In vivo expression of miR-381-3p in dendritic cells (DCs) of TB patients is higher than in DCs of healthy individuals, inversely related to CD1c. Suppression of CD1c expression in bacillus Calmette-Guérin (BCG)-infected DCs was accompanied with upregulation of miR-381-3p, whereas inhibition of miR-381-3p could reverse suppression of CD1c expression and promote T cell responses against BCG infection. Further study indicated that miR-381-3p is also one of the mediators of the immune suppressor IL-10. Collectively, these results demonstrated the mechanism that suppression of CD1c by BCG infection is mediated by miR-381-3p. This finding may provide a novel approach to boost immune responses to M. tuberculosis.
Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, Guangzhou 510515, China; and.
Qian
Q
Wen
Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, Guangzhou 510515, China; and.
Chaoying
C
Zhou
Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, Guangzhou 510515, China; and.
Wenjing
W
Xiong
Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Jing
0000-0002-1671-0715
J
Su
Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, Guangzhou 510515, China; and.
Jianchun
J
He
Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, Guangzhou 510515, China; and.
Shimeng
S
Zhang
Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, Guangzhou 510515, China; and.
Xialin
X
Du
Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, Guangzhou 510515, China; and.
Sudong
S
Liu
Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, Guangzhou 510515, China; and.
Juanjuan
J
Wang
Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, Guangzhou 510515, China; and maryhmz@126.com.
Li
L
Ma
D000465:Algorithms; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D018949:Antigens, CD1 / Q000276:immunology*; D001500:BCG Vaccine; D015153:Blotting, Western; D002469:Cell Separation; D019295:Computational Biology; D003713:Dendritic Cells / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics / Q000276:immunology; D035683:MicroRNAs / Q000276:immunology*; D009169:Mycobacterium tuberculosis; D060888:Real-Time Polymerase Chain Reaction; D014376:Tuberculosis / Q000276:immunology*
D018949:Antigens, CD1; D001500:BCG Vaccine; C437944:CD1C protein, human; D006023:Glycoproteins; C588249:MIRN381 microRNA, human; D035683:MicroRNAs