Differential Expression of miR-146 and miR-155 in Active and Latent Tuberculosis Infection
Abstract
Background: Tuberculosis (TB) is one of the leading causes of death worldwide. Besides, one-third of the world population is infected with Mycobacterium tuberculosis (MTB) while staying clinically asymptomatic; the situation is called latent TB infection (LTBI). MiR-21, miR-31, miR-146a, and miR-155 play an important role in many immune and inflammatory pathways. In the present study the expression levels of MiR-21, miR-31, miR-146a, and miR-155 in peripheral blood mononuclear cells (PBMCs) from patients with active TB, latently infected individuals (LTBI), and healthy controls (HC) were investigated. Participants were recruited at the Bouali Hospital, Zahedan University of Medical Sciences, Zahedan, Iran from 2010 to 2011.
Methods: PBMCs were stimulated with PPD before RNA extraction. TaqMan RT-qPCR assay was used to analyze the expression levels of miRNAs.
Results: The results indicated no significant differences in the expression of miR-21 and miR-31 between different groups; however, in patients with active TB, the expression of miR-21 (P=0.03) and miR-31 (P=0.04) were significantly increased after stimulation with PPD compared to the unstimulated condition. The expression of miR-146 in response to PPD in both LTBI (P=0.02) and TB (P=0.03) groups compared to the HC group was increased. No significant differences were found in the expression level of miR-155 in response to PPD between LTBI and HC groups. However, the fold change was significantly higher in the TB group in comparison with the HC (P=0.03) and LTBI (P=0.05) groups.
Conclusion: The results confirm the main role of miR-146 and miR-155 in TB infection and suggest a role for miR-146 and miR-155 as infection and activation markers in tuberculosis infection, respectively.
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15. Wang C., Yang Sh, Sun G, et al (2011). Comparative miRNA expression pro-files in individuals with latent and active tuberculosis. PloS One, 6 (10): e25832 .
16. Chen DY, Chen YM, Lin Ch, et al (2020). MicroRNA-889 Inhibits Autophagy To Maintain Mycobacterial Survival in Pa-tients with Latent Tuberculosis Infection by Targeting TWEAK. mBio 11 (1): e03045-19.
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21. Liu PT, Wheelwrigh M, Teles R, et al (2012). MicroRNA-21 targets the vitamin D-dependent antimicrobial pathway in leprosy. Nat Med, 18 (2): 267–273.
22. Zhao Z, Hao J, Li X, Chen Y, et al (2019). MiR-21-5p regulates mycobacterial sur-vival and inflammatory responses by targeting Bcl-2 and TLR4 in Mycobacte-rium tuberculosis-infected macrophages. FEBS Lett, 593 (12): 1326–1335.
23. Wang JX, Xu J, Han YF, et al (2015). Diag-nostic values of microRNA-31 in pe-ripheral blood mononuclear cells for pediatric pulmonary tuberculosis in Chinese patients. Genet Mol Res, 14 (4): 17235–17243.
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25. Ghorpade DS, Holla S, Kaveri S, et al (2013). Sonic hedgehog-dependent in-duction of microRNA 31 and mi-croRNA 150 regulates Mycobacterium bovis BCG-driven toll-like receptor 2 signaling. Mol Cell Biol, 33 (3): 543–556.
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27. Wu J, Lu Ch, Diao N, et al (2012). Analysis of microRNA expression profiling iden-tifies miR-155 and miR-155* as potential diagnostic markers for active tuberculo-sis: a preliminary study. Hum Immunol, 73 (1): 31–37.
28. Rajaram MVS, Ni B, Morris JD, et al (2011). Mycobacterium tuberculosis lipoman-nan blocks TNF biosynthesis by regulat-ing macrophage MAPK-activated pro-tein kinase 2 (MK2) and microRNA miR-125b. Proc. Natl Acad Sci USA, 108 (42): 17408–17413.
29. Liu Zh, Zhou G, Deng X, et al (2014). Anal-ysis of miRNA expression profiling in human macrophages responding to My-cobacterium infection: induction of the immune regulator miR-146a. J Infect, 68 (6): 553–561.
30. Spinelli SV, Diaz A, D'Attilio L, et al (2013). Altered microRNA expression levels in mononuclear cells of patients with pul-monary and pleural tuberculosis and their relation with components of the immune response. Mol Immunol, 53 (3): 265–269.
31. Furci L, Schena E, Miotto P, et al (2013) Al-teration of human macrophages mi-croRNA expression profile upon infec-tion with Mycobacterium tuberculosis. Int J Mycobacteriology, 2 (3): 128–134.
32. O’Connell RM, Rao DS, Chaudhuri AA, et al (2010). Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol, 10 (2): 111–122.
33. Hirschberger S, Hinske LC, Kreth S (2018). MiRNAs: dynamic regulators of immune cell functions in inflammation and can-cer. Cancer Lett, 431: 11–21.
34. Taganov KD, Boldin MP, Chang KJ, et al (2006). NF-kappa B-dependent induction of microRNA miR-146, an inhibitor tar-geted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA, 103 (33): 12481–12486.
35. Perry MM, Moscho SA, Williams AE, et al (2008). Rapid changes in microRNA-146a expression negatively regulate the IL-1beta-induced inflammatory re-sponse in human lung alveolar epithelial cells. J Immunol, 180 (8): 5689–5698.
36. Iwai H, Funatogawa K, Matsumura K, et al (2015). MicroRNA-155 knockout mice are susceptible to Mycobacterium tuber-culosis infection. Tuberculosis (Edinb), 95 (1): 246–250.
37. Rothchild AC, Sissons JR, Shafiani Sh, et al (2016). MiR-155-regulated molecular network orchestrates cell fate in the in-nate and adaptive immune response to Mycobacterium tuberculosis. Proc Natl Acad Sci USA, 113 (41): E6172–E6181.
38. Li M, Wang J, Fang Y, et al (2016). mi-croRNA-146a promotes mycobacterial survival in macrophages through sup-pressing nitric oxide production. Sci Rep, 6: 23351.
2. Cohen A, Mathiasen V D, Schön T & Wejse, C (2019). The global prevalence of latent tuberculosis: a systematic re-view and meta-analysis. Eur Respir J, 54 (3): 1900655.
3. Treiber T, Treiber N & Meister G (2019). Regulation of microRNA biogenesis and its crosstalk with other cellular pathways. Nat Rev Mol Cell Biol, 20 (1): 5–20.
4. Mehta A, Baltimore D (2016). MicroRNAs as regulatory elements in immune sys-tem logic. Nat Rev Immunol, 16 (5): 279–294.
5. Adibzadeh Sereshgi MM. Abdollahpour-Alitappeh M, Mahdavi M, et al (2019). Immunologic balance of regulatory T cell/T helper 17 responses in gastroin-testinal infectious diseases: Role of miRNAs. Microb Pathog, 131, 135–143.
6. Chandan K, Gupta M, Sarwat M (2019). Role of Host and Pathogen-Derived Mi-croRNAs in Immune Regulation During Infectious and Inflammatory Diseases. Front Immunol, 10: 3081.
7. Ranjbar R, Hesari Ar, Ghasemi F, et al (2018). Expression of microRNAs and IRAK1 pathway genes are altered in gas-tric cancer patients with Helicobacter pylori infection. J Cell Biochem, 119 (9): 7570-7576.
8. Peng Y, Croce CM (2016). The role of Mi-croRNAs in human cancer. Signal Trans-duct Target Ther, 28 (1): 15004.
9. Fu Y, Yang X, Chen H, Lu Y (2020). Diag-nostic value of miR-145 and its regulato-ry role in macrophage immune re-sponse in tuberculosis. Genet Mol Biol, 43 (2): e20190238.
10. Sabir N, Hussain T, Shah SZA, et al (2018). miRNAs in Tuberculosis: New Avenues for Diagnosis and Host-Directed Ther-apy. Front Microbiol, 29 (9): 602.
11. Sampath P, Periyasamy K M, Ranganathan UD, Bethunaickan R (2021). Monocyte and Macrophage miRNA: Potent Bi-omarker and Target for Host-Directed Therapy for Tuberculosis. Front Immunol, 25 (12): 667206.
12. Ghorpade DS, Leyland R, Kurowska-Stolarska M, et al (2012). N. MicroRNA-155 is required for Mycobacterium bovis BCG-mediated apoptosis of macro-phages. Mol Cell Biol, 32 (12): 2239–2253.
13. Wagh V, Urhekar A, Modi D (2017). Levels of microRNA miR-16 and miR-155 are altered in serum of patients with tuber-culosis and associate with responses to therapy. Tuberculosis (Edinb) 102: 24–30.
14. Lv Y, Guo Sh, Li X, et al (2016). Sputum and serum microRNA-144 levels in patients with tuberculosis before and after treatment. Int J Infect Dis, 43: 68–73.
15. Wang C., Yang Sh, Sun G, et al (2011). Comparative miRNA expression pro-files in individuals with latent and active tuberculosis. PloS One, 6 (10): e25832 .
16. Chen DY, Chen YM, Lin Ch, et al (2020). MicroRNA-889 Inhibits Autophagy To Maintain Mycobacterial Survival in Pa-tients with Latent Tuberculosis Infection by Targeting TWEAK. mBio 11 (1): e03045-19.
17. Quinn SR, O’Neill LA (2011). A trio of mi-croRNAs that control Toll-like receptor signalling. Int Immunol, 23 (7): 421–425.
18. Ajdary S, Riazi-Rad F, Alimohammadian MH (2009). Immune response to Leish-mania antigen in anthroponotic cutane-ous leishmaniasis. J Infect, 59 (2): 139–143.
19. M K, S S, S M (2020). Expression levels of candidate circulating microRNAs in pe-diatric tuberculosis. Pathog Glob Health, 114 (5): 262–270.
20. Zhou M, Yu G, Yang X, et al (2016). Circu-lating microRNAs as biomarkers for the early diagnosis of childhood tuberculo-sis infection. Mol Med Rep, 13 (6): 4620–4626 .
21. Liu PT, Wheelwrigh M, Teles R, et al (2012). MicroRNA-21 targets the vitamin D-dependent antimicrobial pathway in leprosy. Nat Med, 18 (2): 267–273.
22. Zhao Z, Hao J, Li X, Chen Y, et al (2019). MiR-21-5p regulates mycobacterial sur-vival and inflammatory responses by targeting Bcl-2 and TLR4 in Mycobacte-rium tuberculosis-infected macrophages. FEBS Lett, 593 (12): 1326–1335.
23. Wang JX, Xu J, Han YF, et al (2015). Diag-nostic values of microRNA-31 in pe-ripheral blood mononuclear cells for pediatric pulmonary tuberculosis in Chinese patients. Genet Mol Res, 14 (4): 17235–17243.
24. Wang Ch, Yang S, Liu Ch, et al (2018). Screening and identification of four se-rum miRNAs as novel potential bi-omarkers for cured pulmonary tubercu-losis. Tuberclosis (Edinb), 108: 26–34.
25. Ghorpade DS, Holla S, Kaveri S, et al (2013). Sonic hedgehog-dependent in-duction of microRNA 31 and mi-croRNA 150 regulates Mycobacterium bovis BCG-driven toll-like receptor 2 signaling. Mol Cell Biol, 33 (3): 543–556.
26. Kleinsteuber K, Heesch K, Schattling S, et al (2013). Decreased expression of miR-21, miR-26a, miR-29a, and miR-142-3p in CD4+ T cells and peripheral blood from tuberculosis patients. PloS One, 8(4): e61609.
27. Wu J, Lu Ch, Diao N, et al (2012). Analysis of microRNA expression profiling iden-tifies miR-155 and miR-155* as potential diagnostic markers for active tuberculo-sis: a preliminary study. Hum Immunol, 73 (1): 31–37.
28. Rajaram MVS, Ni B, Morris JD, et al (2011). Mycobacterium tuberculosis lipoman-nan blocks TNF biosynthesis by regulat-ing macrophage MAPK-activated pro-tein kinase 2 (MK2) and microRNA miR-125b. Proc. Natl Acad Sci USA, 108 (42): 17408–17413.
29. Liu Zh, Zhou G, Deng X, et al (2014). Anal-ysis of miRNA expression profiling in human macrophages responding to My-cobacterium infection: induction of the immune regulator miR-146a. J Infect, 68 (6): 553–561.
30. Spinelli SV, Diaz A, D'Attilio L, et al (2013). Altered microRNA expression levels in mononuclear cells of patients with pul-monary and pleural tuberculosis and their relation with components of the immune response. Mol Immunol, 53 (3): 265–269.
31. Furci L, Schena E, Miotto P, et al (2013) Al-teration of human macrophages mi-croRNA expression profile upon infec-tion with Mycobacterium tuberculosis. Int J Mycobacteriology, 2 (3): 128–134.
32. O’Connell RM, Rao DS, Chaudhuri AA, et al (2010). Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol, 10 (2): 111–122.
33. Hirschberger S, Hinske LC, Kreth S (2018). MiRNAs: dynamic regulators of immune cell functions in inflammation and can-cer. Cancer Lett, 431: 11–21.
34. Taganov KD, Boldin MP, Chang KJ, et al (2006). NF-kappa B-dependent induction of microRNA miR-146, an inhibitor tar-geted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA, 103 (33): 12481–12486.
35. Perry MM, Moscho SA, Williams AE, et al (2008). Rapid changes in microRNA-146a expression negatively regulate the IL-1beta-induced inflammatory re-sponse in human lung alveolar epithelial cells. J Immunol, 180 (8): 5689–5698.
36. Iwai H, Funatogawa K, Matsumura K, et al (2015). MicroRNA-155 knockout mice are susceptible to Mycobacterium tuber-culosis infection. Tuberculosis (Edinb), 95 (1): 246–250.
37. Rothchild AC, Sissons JR, Shafiani Sh, et al (2016). MiR-155-regulated molecular network orchestrates cell fate in the in-nate and adaptive immune response to Mycobacterium tuberculosis. Proc Natl Acad Sci USA, 113 (41): E6172–E6181.
38. Li M, Wang J, Fang Y, et al (2016). mi-croRNA-146a promotes mycobacterial survival in macrophages through sup-pressing nitric oxide production. Sci Rep, 6: 23351.
| Files | ||
| Issue | Vol 52 No 8 (2023) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v52i8.13414 | |
| Keywords | ||
| Latent TB infection microRNA Mycobacterium tuberculosis PPD Purified protein derivative | ||
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How to Cite
1.
Alijani E, Riazi Rad F, Katebi A, Ajdary S. Differential Expression of miR-146 and miR-155 in Active and Latent Tuberculosis Infection. Iran J Public Health. 2023;52(8):1749-1757.
