microRNA在结核分枝杆菌抗细胞自噬作用中的研究进展
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摘要
结核分枝杆菌(Mycobacteria tuberculosis,MTB)是结核病的致病菌,其感染机体后能在细胞内长期生存并在合适的条件下引发疾病.非氧依赖性杀伤是巨噬细胞清除MTB的重要途径,主要表现为细胞内吞体和溶酶体融合,利用细胞自噬作用清除内部细菌.相应的,MTB可利用多种方式顽强抵抗细胞自噬作用,与细胞共存从而逃避宿主免疫杀伤作用. MicroRNA(miRNA)是一种内源性非编码单链小RNA分子,其能在转录后水平沉默相关基因表达,是介导MTB与炎性细胞许多反应的重要分子.近期研究发现,MTB能够通过诱导巨噬细胞特异表达一些miRNA分子并靶向自噬相关基因,阻碍自噬发生、发展,从而实现MTB的抗细胞自噬作用.本文就miRNA在MTB抗细胞自噬中的作用及机制的研究进展作一综述.
Mycobacteria tuberculosis(MTB) is the pathogen responsible for tuberculosis. It can exist in the infected-macrophages for a long time and trigger the disease when the appropriate conditions arise. The primary way to kill intracellular bacteria is via the oxygen-independent route. In this route, macrophages mainly rid themselves of parasites by autophagy where autophagosomes and lysosomes are fused into autophagolysosomes.However, MTB can resist to autophagy and avoid being killed by the immune system of host cells in several ways, thereby co-existing with the host. MicroRNAs(miRNA) are endogenous non-coding single-chain RNA molecules that can silence related genes expression in a post-transcriptional manner. They are crucial molecules for mediating inflammatory reactions between MTB and inflammatory cells. Recent studies found that MTB can induce the expression of certain specific miRNAs in macrophages and target genes related to autophagy and therefore inhibit triggering and progression of autophagy. This mechanism confers resistance to autophagy. The present review summarizes the role of miRNA in the resistance to autophagy by MTB.
Mycobacteria tuberculosis(MTB) is the pathogen responsible for tuberculosis. It can exist in the infected-macrophages for a long time and trigger the disease when the appropriate conditions arise. The primary way to kill intracellular bacteria is via the oxygen-independent route. In this route, macrophages mainly rid themselves of parasites by autophagy where autophagosomes and lysosomes are fused into autophagolysosomes.However, MTB can resist to autophagy and avoid being killed by the immune system of host cells in several ways, thereby co-existing with the host. MicroRNAs(miRNA) are endogenous non-coding single-chain RNA molecules that can silence related genes expression in a post-transcriptional manner. They are crucial molecules for mediating inflammatory reactions between MTB and inflammatory cells. Recent studies found that MTB can induce the expression of certain specific miRNAs in macrophages and target genes related to autophagy and therefore inhibit triggering and progression of autophagy. This mechanism confers resistance to autophagy. The present review summarizes the role of miRNA in the resistance to autophagy by MTB.
引文
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[30]Duan X,Zhang T,Ding S,et al.MicroRNA-17-5p modulates bacille calmette-guerin growth in RAW264.7 cells by targeting ULK1.Plos One,2015,10(9):e0138011
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[34]Wang J,Yang K,Zhou L,et al.MicroRNA-155 promotes autophagy to eliminate intracellular mycobacteria by targeting Rheb.Plos Pathog,2013,9(10):e1003697
[35]Etna M P,Sinigaglia A,Grassi A,et al.Mycobacterium tuberculosis-induced miR-155 subverts autophagy by targeting ATG3 in human dendritic cells.Plos Pathog,2018,14(1):e1006790
[36]Wagh V,Urhekar A,Modi D.Levels of microRNA miR-16 and miR-155 are altered in serum of patients with tuberculosis and associate with responses to therapy.Tuberculosis(Edinb),2017,102:24-30
[37]Lv Y,Guo S,Li X G,et al.Sputum and serum microRNA-144levels in patients with tuberculosis before and after treatment.International Journal of Infectious Diseases,2016,43:68-73
[2]Spinelli S V,Diaz A,D'attilio L,et al.Altered microRNAexpression levels in mononuclear cells of patients with pulmonary and pleural tuberculosis and their relation with components of the immune response.Molecular Immunology,2013,53(3):265-269
[3]Mehta A,Baltimore D.MicroRNAs as regulatory elements in immune system logic.Nat Rev Immunol,2016,16(5):279-294
[4]Yates L A,Norbury C J,Gilbert R J.The long and short of microRNA.Cell,2013,153(3):516-519
[5]Deretic V,Klionsky D J.Autophagy and inflammation:a special review issue.Autophagy,2018,14(2):179-180
[6]Dong H,Jing W,Runpeng Z,et al.ESAT6 inhibits autophagy flux and promotes BCG proliferation through MTOR.Biochemical and Biophysical Research Communications,2016,477(2):195-201
[7]Kim J K,Kim T S,Basu J,et al.MicroRNA in innate immunity and autophagy during mycobacterial infection.Cellular Microbiology,2017,19(1),doi:10.1111/cmi.12687
[8]Sun K T,Chen M Y,Tu M G,et al.MicroRNA-20a regulates autophagy related protein-ATG16L1 in hypoxia-induced osteoclast differentiation.Bone,2015,73:145-153
[9]He W,Cheng Y.Inhibition of miR-20 promotes proliferation and autophagy in articular chondrocytes by PI3K/AKT/m TORsignaling pathway.Biomed Pharmacother,2018,97:607-615
[10]Liu L,He J,Wei X,et al.MicroRNA-20a-mediated loss of autophagy contributes to breast tumorigenesis by promoting genomic damage and instability.Oncogene,2017,36(42):5874-5884
[11]Guo L,Zhao J,Qu Y,et al.MicroRNA-20a inhibits autophagic process by targeting ATG7 and ATG16L1 and favors mycobacterial survival in macrophage cells.Front Cell Infect Microbiol,2016,6:134
[12]Levine B,Mizushima N,Virgin H W.Autophagy in immunity and inflammation.Nature,2011,469(7330):323-335
[13]Gu X,Gao Y,Mu D G,et al.MiR-23a-5p modulates mycobacterial survival and autophagy during mycobacterium tuberculosis infection through TLR2/MyD88/NF-kappaB pathway by targeting TLR2.Exp Cell Res,2017,354(2):71-77
[14]Banerjee A,Gerondakis S.Coordinating TLR-activated signaling pathways in cells of the immune system.Immunol Cell Biol,2007,85(6):420-424
[15]Du X,Liu B,Luan X,et al.MiR-30 decreases multidrug resistance in human gastric cancer cells by modulating cell autophagy.Exp Ther Med,2018,15(1):599-605
[16]Zhang T,Tian F,Wang J,et al.Endothelial cell autophagy in atherosclerosis is regulated by miR-30-mediated translational control ofATG6.Cell Physiol Biochem,2015,37(4):1369-1378
[17]Chen Z,Wang T,Liu Z,et al.Inhibition of autophagy by miR-30Ainduced by Mycobacteria tuberculosis as a possible mechanism of immune escape in human macrophages.Jpn J Infect Dis,2015,68(5):420-424
[18]Wu Y,Sun Q,Dai L.Immune regulation of miR-30 on the Mycobacterium tuberculosis-induced TLR/MyD88 signaling pathway in THP-1 cells.Exp Ther Med,2017,14(4):3299-3303
[19]Ouimet M,Koster S,Sakowski E,et al.Mycobacterium tuberculosis induces the miR-33 locus to reprogram autophagy and host lipid metabolism.Nat Immunol,2016,17(6):677-686
[20]Pires D,Bernard E M,Pombo J P,et al.Mycobacterium tuberculosis modulates miR-106b-5p to control cathepsin Sexpression resulting in higher pathogen survival and poor T-cell activation.Front Immunol,2017,8:1819
[21]Pawar K,Sharbati J,Einspanier R,et al.Mycobacterium bovis BCG interferes with miR-3619-5p control of cathepsin S in the process of autophagy.Front Cell Infect Microbiol,2016,6:27
[22]Kim J K,Yuk J M,Kim S Y,et al.MicroRNA-125a inhibits autophagy activation and antimicrobial responses during mycobacterial infection.J Immunol,2015,194(11):5355-5365
[23]Hyttinen J M,Niittykoski M,Salminen A,et al.Maturation of autophagosomes and endosomes:a key role for Rab7.Biochim BiophysActa,2013,1833(3):503-510
[24]Kim J K,Lee H M,Park K S,et al.MIR144*inhibits antimicrobial responses against Mycobacterium tuberculosis in human monocytes and macrophages by targeting the autophagy protein DRAM2.Autophagy,2017,13(2):423-441
[25]Guo L,Zhou L,Gao Q,et al.MicroRNA-144-3p inhibits autophagy activation and enhances Bacillus Calmette-Guerin infection by targeting ATG4a in RAW264.7 macrophage cells.Plos One,2017,12(6):e0179772
[26]周林林,郭乐,汤建中,等.miR-144通过靶向Atg4a调控卡介苗和雷帕霉素诱导的RAW264.7细胞自噬.细胞与分子免疫学杂志,2015,31(2):163-167Zhou L L,Guo L,Tang J Z,et al.Chinese Journal of Cellular and Molecular Immunology,2015,31(2):163-167
[27]Sahu S K,Kumar M,Chakraborty S,et al.MicroRNA 26a(miR-26a)/KLF4 and CREB-C/EBPbeta regulate innate immune signaling,the polarization of macrophages and the trafficking of Mycobacterium tuberculosis to lysosomes during infection.Plos Pathog,2017,13(5):e1006410
[28]Ni B,Rajaram M V,Lafuse W P,et al.Mycobacterium tuberculosis decreases human macrophage IFN-gamma responsiveness through miR-132 and miR-26a.J Immunol,2014,193(9):4537-4547
[29]Rahman S M,Janssen R C,Choudhury M,et al.CCAAT/enhancerbinding protein beta(C/EBPbeta)expression regulates dietaryinduced inflammation in macrophages and adipose tissue in mice.J Biol Chem,2012,287(41):34349-34360
[30]Duan X,Zhang T,Ding S,et al.MicroRNA-17-5p modulates bacille calmette-guerin growth in RAW264.7 cells by targeting ULK1.Plos One,2015,10(9):e0138011
[31]Kumar R,Sahu S K,Kumar M,et al.MicroRNA 17-5p regulates autophagy in Mycobacterium tuberculosis-infected macrophages by targeting Mcl-1 and STAT3.Cellular Microbiology,2016,18(5):679-691
[32]Huang J,Jiao J,Xu W,et al.MiR-155 is upregulated in patients with active tuberculosis and inhibits apoptosis of monocytes by targeting FOXO3.Molecular Medicine Reports,2015,12(5):7102-7108
[33]Zhou Z Q,Wang Z K,Zhang L,et al.Role of ESAT-6 in renal injury by regulating microRNA-155 expression via TLR4/MyD88signaling pathway in mice with Mycobacterium tuberculosis infection.Biosci Rep,2017,37(4),pii:BSR20170021.DOI:10.1042/BSR20170021
[34]Wang J,Yang K,Zhou L,et al.MicroRNA-155 promotes autophagy to eliminate intracellular mycobacteria by targeting Rheb.Plos Pathog,2013,9(10):e1003697
[35]Etna M P,Sinigaglia A,Grassi A,et al.Mycobacterium tuberculosis-induced miR-155 subverts autophagy by targeting ATG3 in human dendritic cells.Plos Pathog,2018,14(1):e1006790
[36]Wagh V,Urhekar A,Modi D.Levels of microRNA miR-16 and miR-155 are altered in serum of patients with tuberculosis and associate with responses to therapy.Tuberculosis(Edinb),2017,102:24-30
[37]Lv Y,Guo S,Li X G,et al.Sputum and serum microRNA-144levels in patients with tuberculosis before and after treatment.International Journal of Infectious Diseases,2016,43:68-73