miR-1224 Expression Is Increased in Human Macrophages after Infection with Bacillus Calmette-Guérin (BCG)
Abstract
Tuberculosis (TB) remains a major threat to human health. Understanding the strategies mycobacteria take to overcome immune defense is important in order to control the infection. Micro (mi)RNAs are master regulators of most pathways in the human body. Infection with mycobacterium impacts upon the host metabolic pathways as they are subverted to obtain the nutrition for intracellular TB survival. In this study, we aimed to investigate the effect of Bacillus Calmette-Guérin (BCG) infection on the expression of three miRNAs (miR-1224, -484 and -425), which are important in infection and in the regulation of metabolic pathways. Peripheral blood monocyte-derived macrophage (MDM) cultures were prepared and infected with BCG at a multiplicity of infection (MOI)=10 or left uninfected as a control. 72h post-infection, RNA was extracted from the cultured cells and cDNA synthesis and real-time PCR performed. Expression levels miRNAs were normalized to the levels of U6 snRNA (Rnu6) using the 2–ΔΔCt method. Infection with BCG resulted in a highly significant increase in miR-1224 expression (24.4±3.8-fold induction) in human MDMs. The induction of miR-484 (1.8±0.3-fold increase) and of miR-425 (1.2±0.2-fold increase) was less increased compared to miR-1224. Mycobacterium tolerates a hostile microenvironment by escaping from lysosomal degradation and providing a lipid-rich niche by trigger with and re-pattering host metabolism. This study highlighted the potential roles of miRNAs in host responses upon mycobacterium infection.
- Carmona J, Cruz A, Moreira-Teixeira L, Sousa C, Sousa J, Osorio NS, et al. Mycobacterium tuberculosis Strains Are Differentially Recognized by TLRs with an Impact on the Immune Response. PLoS One 2013; 8(6):e67277.
- Glaziou P, Falzon D, Floyd K, Raviglione M. Global epidemiology of tuberculosis. Semin Respir Crit Care Med 2013; 34(1):3-16.
- Sotgiu, G., G. Sulis, and A. Matteelli, Tuberculosis-a World Health Organization Perspective. Microbiology Spectrum 2017; 5(1).
- Naderi M, Hashemi M, Rezaei M, Safdari A. Association of Genetic Polymorphisms of IFNGR1 with the Risk of Pulmonary Tuberculosis in Zahedan, Southeast Iran. Tuberc Res Treat 2015;. 2015:292505.
- Aryanpur M, Hosseini M, Masjedi MR, Mortaz E, Tabarsi P, Soori H, et al. A randomized controlled trial of smoking cessation methods in patients newly-diagnosed with pulmonary tuberculosis. BMC Infect Dis 2016; 16:369.
- Alipoor SD, Adcock IM, Garssen J, Mortaz E, Varahram M, Mirsaeidi M, et al. The roles of miRNAs as potential biomarkers in lung diseases. Eur J Pharmacol 2016; 791:395-404.
- Cai Y, Yu X, Hu S, Yu J. A brief review on the mechanisms of miRNA regulation. Genomics Proteomics Bioinformatics 2009; 7(4):147-54.
- Farrell D, Shaughnessy RG, Britton L, MacHugh DE, Markey B, Gordon SV. The Identification of Circulating MiRNA in Bovine Serum and Their Potential as Novel Biomarkers of Early Mycobacterium avium subsp paratuberculosis Infection. PLoS One 2015; 10(7):e013431.
- Liu Y, Wang X, Jiang J, Cao Z, Yang B, Cheng X. Modulation of T cell cytokine production by miR-144* with elevated expression in patients with pulmonary tuberculosis. Mol Immunol 2011; 48(9-10):1084-90.
- Chatterjee S, Dwivedi VP, Singh Y, Siddiqui I, Sharma P, Van Kaer L, et al. Early secreted antigen ESAT-6 of Mycobacterium tuberculosis promotes protective T helper 17 cell responses in a toll-like receptor-2-dependent manner. PLoS Pathog 2011; 7(11):e1002378.
- Singh Y, Kaul V, Mehra A, Chatterjee S, Tousif S, Dwivedi VP, et al. Mycobacterium tuberculosis controls microRNA-99b (miR-99b) expression in infected murine dendritic cells to modulate host immunity. J Biol Chem 2013; 288(7):5056-61.
- Rajaram MV, Ni B, Morris JD, Brooks MN, Carlson TK, Bakthavachalu B, et al. Mycobacterium tuberculosis lipomannan blocks TNF biosynthesis by regulating macrophage MAPK-activated protein kinase 2 (MK2) and microRNA miR-125b. Proc Natl Acad Sci U S A 2011; 108(42):17408-13.
- Fu Y, Yi Z, Wu X, Li J, Xu F. Circulating microRNAs in patients with active pulmonary tuberculosis. J Clin Microbiol 2011; 49(12):4246-51.
- O'Connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D. MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci U S A 2007; 104(5):1604-9.
- Wu J, Lu C, Diao N, Zhang S, Wang S, Wang F, et al. Analysis of microRNA expression profiling identifies miR-155 and miR-155* as potential diagnostic markers for active tuberculosis: a preliminary study. Hum Immunol 2012; 73(1):31-7.
- Cooper AM, Torrado E. Protection versus pathology in tuberculosis: recent insights. Curr Opin Immunol 2012; 24(4):431-7.
- Daniel J, Maamar H, Deb C, Sirakova TD, Kolattukudy PE. Mycobacterium tuberculosis uses host triacylglycerol to accumulate lipid droplets and acquires a dormancy-like phenotype in lipid-loaded macrophages. PLoS Pathog 2011; 7(6):e1002093.
- Mehrotra P, Jamwal SV, Saquib N, Sinha N, Siddiqui Z, Manivel V, et al. Pathogenicity of Mycobacterium tuberculosis is expressed by regulating metabolic thresholds of the host macrophage. PLoS Pathog 2014; 10(7):e1004265.
- Eisenreich W, Heesemann J, Rudel T, Goebel W. Metabolic host responses to infection by intracellular bacterial pathogens. Front Cell Infect Microbiol 2013; 3:24.
- Olive AJ, Sassetti CM. Metabolic crosstalk between host and pathogen: sensing, adapting and competing. Nat Rev Microbiol 2016; 14(4):221-34.
- O'Neill LA, Pearce EJ. Immunometabolism governs dendritic cell and macrophage function. J Exp Med 2016; 213(1):15-23.
- Kelly B, O'Neill LA. Metabolic reprogramming in macrophages and dendritic cells in innate immunity. Cell Res 2015; 25(7):771-84.
- Lee W, VanderVen BC, Fahey RJ, Russell DG. Intracellular Mycobacterium tuberculosis exploits host-derived fatty acids to limit metabolic stress. J Biol Chem 2013; 288(10):6788-6800.
- Ouimet M, Koster S, Sakowski E, Ramkhelawon B, van Solingen C, Oldebeken S, et al., Mycobacterium tuberculosis induces the miR-33 locus to reprogram autophagy and host lipid metabolism. Nat Immunol 2016; 17(6):677-86.
- Bettencourt P, Pires D, Anes E. Immunomodulating microRNAs of mycobacterial infections. Tuberculosis (Edinb) 2016; 97:1-7.
- Kumar M, Sahu SK, Kumar R, Subuddhi A, Maji RK, Jana K, et al. MicroRNA let-7 modulates the immune response to Mycobacterium tuberculosis infection via control of A20, an inhibitor of the NF-kappaB pathway. Cell Host Microbe 2015; 17(3):345-56.
- Niu Y, Mo D, Qin L, Wang C, Li A, Zhao X, et al. Lipopolysaccharide‐induced miR‐1224 negatively regulates tumour necrosis factor‐α gene expression by modulating Sp1. Immunology 2011; 133(1):8-20.
- Sibley CR, Seow Y, Curtis H, Weinberg MS, Wood MJ. Silencing of Parkinson's disease-associated genes with artificial mirtron mimics of miR-1224. Nucleic Acids Res 2012; 40(19):9863-75.
- Wang K, Long B, Jiao JQ, Wang JX, Liu JP, et al., miR-484 regulates mitochondrial network through targeting Fis1. Nat Commun 2012; 3:781.
- Barwari T, Skroblin P, Mayr M. When Sweet Turns Salty: Glucose-Induced Suppression of Atrial Natriuretic Peptide by MicroRNA-425. J Am Coll Cardiol 2016; 67(7):813-6.
- Sarir H, Mortaz E, Karimi K, Kraneveld AD, Rahman I, Caldenhoven E, et al. Cigarette smoke regulates the expression of TLR4 and IL-8 production by human macrophages. J Inflamm (Lond) 2009; 6(1):12.
- Nuutila J, Lilius EM. Flow cytometric quantitative determination of ingestion by phagocytes needs the distinguishing of overlapping populations of binding and ingesting cells. Cytometry A 2005; 65(2):93-102.
- Furci L, Schena E, Miotto P, Cirillo DM. Alteration of human macrophages microRNA expression profile upon infection with Mycobacterium tuberculosis. Int J Mycobacteriol 2013; 2(3):128-34.
- Zheng L, Leung E, Lee N, Lui G, To KF, Chan RC, et al. Differential microRNA expression in human macrophages with Mycobacterium tuberculosis infection of Beijing/W and non-Beijing/W strain types. PLoS One 2015; 10(6):e0126018.
- Wang C, Yang S, Sun G, Tang X, Lu S, Neyrolles O, et al. Comparative miRNA expression profiles in individuals with latent and active tuberculosis. PLoS One 2011; 6(10):e25832.
- Elizabeth MC, Hernández de la Cruz ON, Mauricio CA. Infection of J774A. 1 with different Mycobacterium species induces differential immune and miRNA related responses. Microbiol Immunol 2016; 60(5):356-63.
- Rajaram MV, Ni B, Morris JD, Brooks MN, Carlson TK, Bakthavachalu B, et al. Mycobacterium tuberculosis lipomannan blocks TNF biosynthesis by regulating macrophage MAPK-activated protein kinase 2 (MK2) and microRNA miR-125b. Proc Natl Acad Sci U S A 2011; 108(42):17408-17413.
- Cherni I, Weiss GJ. miRNAs in lung cancer: large roles for small players. Future Oncol 2011; 7(9):1045-55.
- Vickers KC, Sethupathy P, Baran-Gale J, Remaley AT. Complexity of microRNA function and the role of isomiRs in lipid homeostasis. J Lipid Res 2013; 54(5):1182-91.
- Vickers KC, Sethupathy P, Baran-Gale J, Remaley AT. Complexity of microRNA function and the role of isomiRs in lipid homeostasis. J Lipid Res 2013; 54(5):1182-91.
- Chan J, Flynn J. The immunological aspects of latency in tuberculosis. Clin Immunol 2004; 110(1):2-12.
- Dorhoi A, Kaufmann SH. Tumor necrosis factor alpha in mycobacterial infection. Semin Immunol 2014; 26(3):203-9.
- Harris J, Hope JC, Keane J. Tumor necrosis factor blockers influence macrophage responses to Mycobacterium tuberculosis. J Infect Dis 2008; 198(12):1842-50.
- Balcewicz-Sablinska MK, Keane J, Kornfeld H, Remold HG. Pathogenic Mycobacterium tuberculosis evades apoptosis of host macrophages by release of TNF-R2, resulting in inactivation of TNF-alpha. J Immunol 1998; 161(5):2636-41.
- Spira A, Carroll JD, Liu G, Aziz Z, Shah V, Kornfeld H, et al. Apoptosis genes in human alveolar macrophages infected with virulent or attenuated Mycobacterium tuberculosis: a pivotal role for tumor necrosis factor. Am J Respir Cell Mol Biol 2003; 29(5):545-51.
- Winau F, Weber S, Sad S, de Diego J, Hoops SL, Breiden B, et al. Apoptotic vesicles crossprime CD8 T cells and protect against tuberculosis. Immunity 2006; 24(1):105-17.
- Elizabeth MC, Hernández de la Cruz ON, Mauricio CA. Infection of J774A.1 with different Mycobacterium species induces differential immune and miRNA-related responses. Microbiol Immunol 2016; 60(5):356-63.
- Kurtz S, McKinnon KP, Runge MS, Ting JP, Braunstein M. The SecA2 secretion factor of Mycobacterium tuberculosis promotes growth in macrophages and inhibits the host immune response. Infect Immun 2006; 74(12):6855-64.
- Reed MB, Domenech P, Manca C, Su H, Barczak AK, Kreiswirth BN, et al. A glycolipid of hypervirulent tuberculosis strains that inhibits the innate immune response. Nature 2004; 431(7004):84-7.
- Stanley SA, Raghavan S, Hwang WW, Cox JS. Acute infection and macrophage subversion by Mycobacterium tuberculosis require a specialized secretion system. Proc Natl Acad Sci U S A 2003; 100(22):13001-6.
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Issue | Vol 17, No 3 (2018) | |
Section | Original Article(s) | |
Keywords | ||
Macrophages miR-1224 miR-484 miR-425 Monocyte-derived macrophage Tuberculosis |
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