IMMUNE NETWORK

The Korean Association of Immunobiologists (대한면역학회)
권호 표지
DOI QR코드

DOI QR Code

Host-Pathogen Interactions Operative during Mycobacteroides abscessus Infection

  • Eun-Jin Park (Department of Microbiology, Chungnam National University College of Medicine) ;
  • Prashanta Silwal (Department of Microbiology, Chungnam National University College of Medicine) ;
  • Eun-Kyeong Jo (Department of Microbiology, Chungnam National University College of Medicine)
  • Received : 2021.08.31
  • Accepted : 2021.12.09
  • Published : 2021.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Mycobacteroides abscessus (previously Mycobacterium abscessus; Mabc), one of rapidly growing nontuberculous mycobacteria (NTM), is an important pathogen of NTM pulmonary diseases (NTM-PDs) in both immunocompetent and immunocompromised individuals. Mabc infection is chronic and often challenging to treat due to drug resistance, motivating the development of new therapeutics. Despite this, there is a lack of understanding of the relationship between Mabc and the immune system. This review highlights recent progress in the molecular architecture of Mabc and host interactions. We discuss several microbial components that take advantage of host immune defenses, host defense pathways that can overcome Mabc pathogenesis, and how host-pathogen interactions determine the outcomes of Mabc infection. Understanding the molecular mechanisms underlying host-pathogen interactions during Mabc infection will enable the identification of biomarkers and/or drugs to control immune pathogenesis and protect against NTM infection.

Keywords

Acknowledgement

We are indebted to current and past members of our laboratory for discussions and investigations that contributed to this article. This work was supported by Chungnam National University Hospital Research Fund, 2021 and the National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MSIP) (No. 2017R1A5A2015385). We apologize to colleagues whose work and publications could not be referenced owing to space constraints.

References

  1. Johansen MD, Herrmann JL, Kremer L. Non-tuberculous mycobacteria and the rise of Mycobacterium abscessus. Nat Rev Microbiol 2020;18:392-407. https://doi.org/10.1038/s41579-020-0331-1
  2. Victoria L, Gupta A, Gomez JL, Robledo J. Mycobacterium abscessus complex: a review of recent developments in an emerging pathogen. Front Cell Infect Microbiol 2021;11:659997.
  3. Minias A, Zukowska L, Lach J, Jagielski T, Strapagiel D, Kim SY, Koh WJ, Adam H, Bittner R, Truden S, et al. Subspecies-specific sequence detection for differentiation of Mycobacterium abscessus complex. Sci Rep 2020;10:16415.
  4. Tortoli E, Kohl TA, Brown-Elliott BA, Trovato A, Leao SC, Garcia MJ, Vasireddy S, Turenne CY, Griffith DE, Philley JV, et al. Emended description of Mycobacterium abscessus, Mycobacterium abscessus subsp. abscessus and Mycobacteriumabscessus subsp. bolletii and designation of Mycobacteriumabscessus subsp. massiliense comb. nov. Int J Syst Evol Microbiol 2016;66:4471-4479. https://doi.org/10.1099/ijsem.0.001376
  5. Schiff HF, Jones S, Achaiah A, Pereira A, Stait G, Green B. Clinical relevance of non-tuberculous mycobacteria isolated from respiratory specimens: seven year experience in a UK hospital. Sci Rep 2019;9:1730.
  6. Flight WG, Hough NE, Chapman SJ. Outcomes of pulmonary Mycobacterium abscessus infection. Int J Mycobacteriol 2020;9:48-52. https://doi.org/10.4103/ijmy.ijmy_3_20
  7. Medjahed H, Gaillard JL, Reyrat JM. Mycobacterium abscessus: a new player in the mycobacterial field. Trends Microbiol 2010;18:117-123. https://doi.org/10.1016/j.tim.2009.12.007
  8. Degiacomi G, Sammartino JC, Chiarelli LR, Riabova O, Makarov V, Pasca MR. Mycobacterium abscessus, an emerging and worrisome pathogen among cystic fibrosis patients. Int J Mol Sci 2019;20:5868.
  9. Ho D, Belmonte O, Andre M, Gazaille V, Perisson C, Gachelin E, Allyn J, Payet A, Coolen-Allou N. High prevalence of nontuberculous mycobacteria in cystic fibrosis patients in tropical French Reunion Island. Pediatr Infect Dis J 2021;40:e120-e122. https://doi.org/10.1097/INF.0000000000002999
  10. Leung JM, Olivier KN. Nontuberculous mycobacteria: the changing epidemiology and treatment challenges in cystic fibrosis. Curr Opin Pulm Med 2013;19:662-669. https://doi.org/10.1097/MCP.0b013e328365ab33
  11. Bastian S, Veziris N, Roux AL, Brossier F, Gaillard JL, Jarlier V, Cambau E. Assessment of clarithromycin susceptibility in strains belonging to the Mycobacterium abscessus group by erm(41) and rrl sequencing. Antimicrob Agents Chemother 2011;55:775-781. https://doi.org/10.1128/AAC.00861-10
  12. Honda JR, Alper S, Bai X, Chan ED. Acquired and genetic host susceptibility factors and microbial pathogenic factors that predispose to nontuberculous mycobacterial infections. Curr Opin Immunol 2018;54:66-73. https://doi.org/10.1016/j.ceb.2018.04.007
  13. Adjemian J, Frankland TB, Daida YG, Honda JR, Olivier KN, Zelazny A, Honda S, Prevots DR. Epidemiology of nontuberculous mycobacterial lung disease and tuberculosis, Hawaii, USA. Emerg Infect Dis 2017;23:439-447. https://doi.org/10.3201/eid2303.161827
  14. Crilly NP, Ayeh SK, Karakousis PC. The new frontier of host-directed therapies for Mycobacterium avium complex. Front Immunol 2021;11:623119.
  15. Lee MR, Sheng WH, Hung CC, Yu CJ, Lee LN, Hsueh PR. Mycobacterium abscessus complex infections in humans. Emerg Infect Dis 2015;21:1638-1646. https://doi.org/10.3201/2109.141634
  16. Berube BJ, Castro L, Russell D, Ovechkina Y, Parish T. Novel screen to assess bactericidal activity of compounds against non-replicating Mycobacterium abscessus. Front Microbiol 2018;9:2417.
  17. Fangous MS, Mougari F, Gouriou S, Calvez E, Raskine L, Cambau E, Payan C, Hery-Arnaud G. Classification algorithm for subspecies identification within the Mycobacterium abscessus species, based on matrix-assisted laser desorption ionization-time of flight mass spectrometry. J Clin Microbiol 2014;52:3362-3369. https://doi.org/10.1128/JCM.00788-14
  18. To K, Cao R, Yegiazaryan A, Owens J, Venketaraman V. General overview of nontuberculous mycobacteria opportunistic pathogens: Mycobacterium avium and Mycobacterium abscessus. J Clin Med 2020;9:2541.
  19. Griffin I, Schmitz A, Oliver C, Pritchard S, Zhang G, Rico E, Davenport E, Llau A, Moore E, Fernandez D, et al. Outbreak of tattoo-associated nontuberculous mycobacterial skin infections. Clin Infect Dis 2019;69:949-955. https://doi.org/10.1093/cid/ciy979
  20. Lee H, Myung W, Lee EM, Kim H, Jhun BW. Mortality and prognostic factors of nontuberculous mycobacterial infection in Korea: a population-based comparative study. Clin Infect Dis 2021;72:e610-e619. https://doi.org/10.1093/cid/ciaa1381
  21. Kothavade RJ, Dhurat RS, Mishra SN, Kothavade UR. Clinical and laboratory aspects of the diagnosis and management of cutaneous and subcutaneous infections caused by rapidly growing mycobacteria. Eur J Clin Microbiol Infect Dis 2013;32:161-188. https://doi.org/10.1007/s10096-012-1766-8
  22. Renna M, Schaffner C, Brown K, Shang S, Tamayo MH, Hegyi K, Grimsey NJ, Cusens D, Coulter S, Cooper J, et al. Azithromycin blocks autophagy and may predispose cystic fibrosis patients to mycobacterial infection. J Clin Invest 2011;121:3554-3563. https://doi.org/10.1172/JCI46095
  23. Kim HY, Kim BJ, Kook Y, Yun YJ, Shin JH, Kim BJ, Kook YH. Mycobacterium massiliense is differentiated from Mycobacterium abscessus and Mycobacterium bolletii by erythromycin ribosome methyltransferase gene (erm) and clarithromycin susceptibility patterns. Microbiol Immunol 2010;54:347-353. https://doi.org/10.1111/j.1348-0421.2010.00221.x
  24. Choi GE, Shin SJ, Won CJ, Min KN, Oh T, Hahn MY, Lee K, Lee SH, Daley CL, Kim S, et al. Macrolide treatment for Mycobacterium abscessus and Mycobacterium massiliense infection and inducible resistance. Am J Respir Crit Care Med 2012;186:917-925. https://doi.org/10.1164/rccm.201111-2005OC
  25. Gloag ES, Wozniak DJ, Stoodley P, Hall-Stoodley L. Mycobacterium abscessus biofilms have viscoelastic properties which may contribute to their recalcitrance in chronic pulmonary infections. Sci Rep 2021;11:5020.
  26. Bryant JM, Brown KP, Burbaud S, Everall I, Belardinelli JM, Rodriguez-Rincon D, Grogono DM, Peterson CM, Verma D, Evans IE, et al. Stepwise pathogenic evolution of Mycobacterium abscessus. Science 2021;372:eabb8699.
  27. Bryant JM, Grogono DM, Rodriguez-Rincon D, Everall I, Brown KP, Moreno P, Verma D, Hill E, Drijkoningen J, Gilligan P, et al. Emergence and spread of a human-transmissible multidrug-resistant nontuberculous mycobacterium. Science 2016;354:751-757. https://doi.org/10.1126/science.aaf8156
  28. Yoon JK, Kim TS, Kim JI, Yim JJ. Whole genome sequencing of nontuberculous mycobacterium (NTM) isolates from sputum specimens of co-habiting patients with NTM pulmonary disease and NTM isolates from their environment. BMC Genomics 2020;21:322.
  29. Caverly LJ, Caceres SM, Fratelli C, Happoldt C, Kidwell KM, Malcolm KC, Nick JA, Nichols DP. Mycobacterium abscessus morphotype comparison in a murine model. PLoS One 2015;10:e0117657.
  30. Roux AL, Viljoen A, Bah A, Simeone R, Bernut A, Laencina L, Deramaudt T, Rottman M, Gaillard JL, Majlessi L, et al. The distinct fate of smooth and rough Mycobacterium abscessus variants inside macrophages. Open Biol 2016;6:160185.
  31. Whang J, Back YW, Lee KI, Fujiwara N, Paik S, Choi CH, Park JK, Kim HJ. Mycobacterium abscessus glycopeptidolipids inhibit macrophage apoptosis and bacterial spreading by targeting mitochondrial cyclophilin D. Cell Death Dis 2017;8:e3012.
  32. Kim JK, Silwal P, Jo EK. Host-pathogen dialogues in autophagy, apoptosis, and necrosis during mycobacterial infection. Immune Netw 2020;20:e37.
  33. Honda JR, Hess T, Carlson R, Kandasamy P, Nieto Ramirez LM, Norton GJ, Virdi R, Islam MN, Mehaffy C, Hasan NA, et al. Nontuberculous mycobacteria show differential infectivity and use phospholipids to antagonize LL-37. Am J Respir Cell Mol Biol 2020;62:354-363. https://doi.org/10.1165/rcmb.2018-0278OC
  34. Yuk JM, Shin DM, Lee HM, Yang CS, Jin HS, Kim KK, Lee ZW, Lee SH, Kim JM, Jo EK. Vitamin D3 induces autophagy in human monocytes/macrophages via cathelicidin. Cell Host Microbe 2009;6:231-243. https://doi.org/10.1016/j.chom.2009.08.004
  35. Dumas E, Christina Boritsch E, Vandenbogaert M, Rodriguez de la Vega RC, Thiberge JM, Caro V, Gaillard JL, Heym B, Girard-Misguich F, Brosch R, et al. Mycobacterial pan-genome analysis suggests important role of plasmids in the radiation of Type VII secretion systems. Genome Biol Evol 2016;8:387-402. https://doi.org/10.1093/gbe/evw001
  36. Abdallah AM, Gey van Pittius NC, Champion PA, Cox J, Luirink J, Vandenbroucke-Grauls CM, Appelmelk BJ, Bitter W. Type VII secretion--mycobacteria show the way. Nat Rev Microbiol 2007;5:883-891. https://doi.org/10.1038/nrmicro1773
  37. Newton-Foot M, Warren RM, Sampson SL, van Helden PD, Gey van Pittius NC. The plasmid-mediated evolution of the mycobacterial ESX (Type VII) secretion systems. BMC Evol Biol 2016;16:62.
  38. Gey van Pittius NC, Sampson SL, Lee H, Kim Y, van Helden PD, Warren RM. Evolution and expansion of the Mycobacterium tuberculosis PE and PPE multigene families and their association with the duplication of the ESAT-6 (esx) gene cluster regions. BMC Evol Biol 2006;6:95.
  39. Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CE 3rd, et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 1998;393:537-544.
  40. Kim YS, Yang CS, Nguyen LT, Kim JK, Jin HS, Choe JH, Kim SY, Lee HM, Jung M, Kim JM, et al. Mycobacterium abscessus ESX-3 plays an important role in host inflammatory and pathological responses during infection. Microbes Infect 2017;19:5-17. https://doi.org/10.1016/j.micinf.2016.09.001
  41. Laencina L, Dubois V, Le Moigne V, Viljoen A, Majlessi L, Pritchard J, Bernut A, Piel L, Roux AL, Gaillard JL, et al. Identification of genes required for Mycobacterium abscessus growth in vivo with a prominent role of the ESX-4 locus. Proc Natl Acad Sci U S A 2018;115:E1002-E1011. https://doi.org/10.1073/pnas.1713195115
  42. Melly G, Purdy GE. MmpL proteins in physiology and pathogenesis of M. tuberculosis. Microorganisms 2019;7:70.
  43. Dubois V, Viljoen A, Laencina L, Le Moigne V, Bernut A, Dubar F, Blaise M, Gaillard JL, Guerardel Y, Kremer L, et al. MmpL8MAB controls Mycobacterium abscessus virulence and production of a previously unknown glycolipid family. Proc Natl Acad Sci U S A 2018;115:E10147-E10156. https://doi.org/10.1073/pnas.1812984115
  44. Bakala N'Goma JC, Le Moigne V, Soismier N, Laencina L, Le Chevalier F, Roux AL, Poncin I, Serveau-Avesque C, Rottman M, Gaillard JL, et al. Mycobacterium abscessus phospholipase C expression is induced during coculture within amoebae and enhances M. abscessus virulence in mice. Infect Immun 2015;83:780-791. https://doi.org/10.1128/IAI.02032-14
  45. Becker K, Haldimann K, Selchow P, Reinau LM, Dal Molin M, Sander P. Lipoprotein glycosylation by protein-o-mannosyltransferase (MAB_1122c) contributes to low cell envelope permeability and antibiotic resistance of Mycobacterium abscessus. Front Microbiol 2017;8:2123.
  46. Lee SJ, Jang JH, Yoon GY, Kang DR, Park HJ, Shin SJ, Han HD, Kang TH, Park WS, Yoon YK, et al. Mycobacterium abscessus D-alanyl-D-alanine dipeptidase induces the maturation of dendritic cells and promotes Th1-biased immunity. BMB Rep 2016;49:554-559. https://doi.org/10.5483/BMBRep.2016.49.10.080
  47. Le Moigne V, Belon C, Goulard C, Accard G, Bernut A, Pitard B, Gaillard JL, Kremer L, Herrmann JL, Blanc-Potard AB. MgtC as a host-induced factor and vaccine candidate against Mycobacterium abscessus infection. Infect Immun 2016;84:2895-2903. https://doi.org/10.1128/IAI.00359-16
  48. Halloum I, Carrere-Kremer S, Blaise M, Viljoen A, Bernut A, Le Moigne V, Vilcheze C, Guerardel Y, Lutfalla G, Herrmann JL, et al. Deletion of a dehydratase important for intracellular growth and cording renders rough Mycobacterium abscessus avirulent. Proc Natl Acad Sci U S A 2016;113:E4228-E4237. https://doi.org/10.1073/pnas.1605477113
  49. Kilinc G, Saris A, Ottenhoff TH, Haks MC. Host-directed therapy to combat mycobacterial infections. Immunol Rev 2021;301:62-83. https://doi.org/10.1111/imr.12951
  50. Prasla Z, Sutliff RL, Sadikot RT. Macrophage signaling pathways in pulmonary nontuberculous mycobacteria infections. Am J Respir Cell Mol Biol 2020;63:144-151. https://doi.org/10.1165/rcmb.2019-0241TR
  51. Kawai T, Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity 2011;34:637-650. https://doi.org/10.1016/j.immuni.2011.05.006
  52. Dolasia K, Bisht MK, Pradhan G, Udgata A, Mukhopadhyay S. TLRs/NLRs: Shaping the landscape of host immunity. Int Rev Immunol 2018;37:3-19. https://doi.org/10.1080/08830185.2017.1397656
  53. Feng H, Zhang YB, Gui JF, Lemon SM, Yamane D. Interferon regulatory factor 1 (IRF1) and anti-pathogen innate immune responses. PLoS Pathog 2021;17:e1009220.
  54. Tak PP, Firestein GS. NF-kappaB: a key role in inflammatory diseases. J Clin Invest 2001;107:7-11. https://doi.org/10.1172/JCI11830
  55. Kim BR, Kim BJ, Kook YH, Kim BJ. Mycobacterium abscessus infection leads to enhanced production of type 1 interferon and NLRP3 inflammasome activation in murine macrophages via mitochondrial oxidative stress. PLoS Pathog 2020;16:e1008294.
  56. Feng Z, Bai X, Wang T, Garcia C, Bai A, Li L, Honda JR, Nie X, Chan ED. Differential responses by human macrophages to infection with Mycobacterium tuberculosis and non-tuberculous mycobacteria. Front Microbiol 2020;11:116.
  57. Swanson KV, Deng M, Ting JP. The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat Rev Immunol 2019;19:477-489. https://doi.org/10.1038/s41577-019-0165-0
  58. Paik S, Kim JK, Silwal P, Sasakawa C, Jo EK. An update on the regulatory mechanisms of NLRP3 inflammasome activation. Cell Mol Immunol 2021;18:1141-1160. https://doi.org/10.1038/s41423-021-00670-3
  59. Lee HM, Yuk JM, Kim KH, Jang J, Kang G, Park JB, Son JW, Jo EK. Mycobacterium abscessus activates the NLRP3 inflammasome via Dectin-1-Syk and p62/SQSTM1. Immunol Cell Biol 2012;90:601-610. https://doi.org/10.1038/icb.2011.72
  60. Le Moigne V, Roux AL, Jobart-Malfait A, Blanc L, Chaoui K, Burlet-Schiltz O, Gaillard JL, Canaan S, Nigou J, Herrmann JL. TLR2-activating fraction from Mycobacterium abscessus rough variant demonstrates vaccine and diagnostic potential. Front Cell Infect Microbiol 2020;10:432.
  61. Kim JS, Kang MJ, Kim WS, Han SJ, Kim HM, Kim HW, Kwon KW, Kim SJ, Cha SB, Eum SY, et al. Essential engagement of Toll-like receptor 2 in initiation of early protective Th1 response against rough variants of Mycobacterium abscessus. Infect Immun 2015;83:1556-1567. https://doi.org/10.1128/IAI.02853-14
  62. Davidson LB, Nessar R, Kempaiah P, Perkins DJ, Byrd TF. Mycobacterium abscessus glycopeptidolipid prevents respiratory epithelial TLR2 signaling as measured by H𻋒 gene expression and IL-8 release. PLoS One 2011;6:e29148.
  63. Ruangkiattikul N, Rys D, Abdissa K, Rohde M, Semmler T, Tegtmeyer PK, Kalinke U, Schwarz C, Lewin A, Goethe R. Type I interferon induced by TLR2-TLR4-MyD88-TRIF-IRF3 controls Mycobacterium abscessus subsp. abscessus persistence in murine macrophages via nitric oxide. Int J Med Microbiol 2019;309:307-318. https://doi.org/10.1016/j.ijmm.2019.05.007
  64. Kim TS, Kim YS, Yoo H, Park YK, Jo EK. Mycobacterium massiliense induces inflammatory responses in macrophages through Toll-like receptor 2 and c-Jun N-terminal kinase. J Clin Immunol 2014;34:212-223. https://doi.org/10.1007/s10875-013-9978-y
  65. Lee JY, Lee MS, Kim DJ, Yang SJ, Lee SJ, Noh EJ, Shin SJ, Park JH. Nucleotide-binding oligomerization domain 2 contributes to limiting growth of Mycobacterium abscessus in the lung of mice by regulating cytokines and nitric oxide production. Front Immunol 2017;8:1477.
  66. Jang MA, Kim SY, Jeong BH, Park HY, Jeon K, Kim JW, Ki CS, Koh WJ. Association of CFTR gene variants with nontuberculous mycobacterial lung disease in a Korean population with a low prevalence of cystic fibrosis. J Hum Genet 2013;58:298-303. https://doi.org/10.1038/jhg.2013.19
  67. Bernut A, Dupont C, Ogryzko NV, Neyret A, Herrmann JL, Floto RA, Renshaw SA, Kremer L. CFTR protects against Mycobacterium abscessus infection by fine-tuning host oxidative defenses. Cell Rep 2019;26:1828-1840.e4. https://doi.org/10.1016/j.celrep.2019.01.071
  68. Johansen MD, Kremer L. CFTR depletion confers hypersusceptibility to Mycobacterium fortuitum in a zebrafish model. Front Cell Infect Microbiol 2020;10:357.
  69. Kunzi L, Easter M, Hirsch MJ, Krick S. Cystic fibrosis lung disease in the aging population. Front Pharmacol 2021;12:601438.
  70. Mall MA. Unplugging mucus in cystic fibrosis and chronic obstructive pulmonary disease. Ann Am Thorac Soc 2016;13 Suppl 2:S177-S185.
  71. Hoyos-Bachiloglu R, Chou J, Sodroski CN, Beano A, Bainter W, Angelova M, Al Idrissi E, Habazi MK, Alghamdi HA, Almanjomi F, et al. A digenic human immunodeficiency characterized by IFNAR1 and IFNGR2 mutations. J Clin Invest 2017;127:4415-4420. https://doi.org/10.1172/JCI93486
  72. Shu CC, Wu LS, Wu MF, Lai HC, Wang PH, Cheng SL, Wang JY, Yu CJ. Mono- and poly-functional T cells in nontuberculous mycobacteria lung disease patients: implications in analyzing risk of disease progression. Cytokine 2019;120:176-185. https://doi.org/10.1016/j.cyto.2019.05.001
  73. Kim SY, Koh WJ, Kim YH, Jeong BH, Park HY, Jeon K, Kim JS, Cho SN, Shin SJ. Importance of reciprocal balance of T cell immunity in Mycobacterium abscessus complex lung disease. PLoS One 2014;9:e109941.
  74. Quan H, Kim J, Na YR, Kim JH, Kim BJ, Kim BJ, Hong JJ, Hwang ES, Seok SH. Human cytomegalovirus-induced interleukin-10 production promotes the proliferation of Mycobacterium massiliense in macrophages. Front Immunol 2020;11:518605.
  75. Zhang C, Asif H, Holt GE, Griswold AJ, Campos M, Bejarano P, Fregien NL, Mirsaeidi M. Mycobacterium abscessus-bronchial epithelial cells cross-talk through type I interferon Signaling. Front Immunol 2019;10:2888.
  76. Bernut A, Nguyen-Chi M, Halloum I, Herrmann JL, Lutfalla G, Kremer L. Mycobacterium abscessus-induced granuloma formation is strictly dependent on TNF signaling and neutrophil trafficking. PLoS Pathog 2016;12:e1005986.
  77. Brode SK, Jamieson FB, Ng R, Campitelli MA, Kwong JC, Paterson JM, Li P, Marchand-Austin A, Bombardier C, Marras TK. Increased risk of mycobacterial infections associated with anti-rheumatic medications. Thorax 2015;70:677-682. https://doi.org/10.1136/thoraxjnl-2014-206470
  78. Kim YJ, Lee SH, Jeon SM, Silwal P, Seo JY, Hanh BT, Park JW, Whang J, Lee MJ, Heo JY, et al. Sirtuin 3 is essential for host defense against Mycobacterium abscessus infection through regulation of mitochondrial homeostasis. Virulence 2020;11:1225-1239. https://doi.org/10.1080/21505594.2020.1809961
  79. Paik S, Kim JK, Chung C, Jo EK. Autophagy: a new strategy for host-directed therapy of tuberculosis. Virulence 2019;10:448-459. https://doi.org/10.1080/21505594.2018.1536598
  80. Deretic V. Autophagy in inflammation, infection, and immunometabolism. Immunity 2021;54:437-453. https://doi.org/10.1016/j.immuni.2021.01.018
  81. Rao L, Eissa NT. Autophagy in pulmonary innate immunity. J Innate Immun 2020;12:21-30. https://doi.org/10.1159/000497414
  82. Kim YS, Silwal P, Kim SY, Yoshimori T, Jo EK. Autophagy-activating strategies to promote innate defense against mycobacteria. Exp Mol Med 2019;51:1-10. https://doi.org/10.1038/s12276-019-0290-7
  83. Riebisch AK, Muhlen S, Beer YY, Schmitz I. Autophagy-A story of bacteria interfering with the host cell degradation machinery. Pathogens 2021;10:110.
  84. Chauhan S, Kumar S, Jain A, Ponpuak M, Mudd MH, Kimura T, Choi SW, Peters R, Mandell M, Bruun JA, et al. TRIMs and galectins globally cooperate and TRIM16 and galectin-3 co-direct autophagy in endomembrane damage homeostasis. Dev Cell 2016;39:13-27. https://doi.org/10.1016/j.devcel.2016.08.003
  85. Chai Q, Wang X, Qiang L, Zhang Y, Ge P, Lu Z, Zhong Y, Li B, Wang J, Zhang L, et al. A Mycobacterium tuberculosis surface protein recruits ubiquitin to trigger host xenophagy. Nat Commun 2019;10:1973.
  86. Watson RO, Bell SL, MacDuff DA, Kimmey JM, Diner EJ, Olivas J, Vance RE, Stallings CL, Virgin HW, Cox JS. The cytosolic sensor cGAS detects Mycobacterium tuberculosis DNA to induce type I interferons and activate autophagy. Cell Host Microbe 2015;17:811-819. https://doi.org/10.1016/j.chom.2015.05.004
  87. Martinez J, Malireddi RK, Lu Q, Cunha LD, Pelletier S, Gingras S, Orchard R, Guan JL, Tan H, Peng J, et al. Molecular characterization of LC3-associated phagocytosis reveals distinct roles for Rubicon, NOX2 and autophagy proteins. Nat Cell Biol 2015;17:893-906. https://doi.org/10.1038/ncb3192
  88. Silwal P, Kim IS, Jo EK. Autophagy and host defense in nontuberculous mycobacterial infection. Front Immunol 2021;12:728742.
  89. Shamaei M, Mirsaeidi M. Nontuberculous mycobacteria, macrophages, and host innate immune response. Infect Immun 2021;89:e0081220.
  90. Zullo AJ, Lee S. Mycobacterial induction of autophagy varies by species and occurs independently of mammalian target of rapamycin inhibition. J Biol Chem 2012;287:12668-12678. https://doi.org/10.1074/jbc.M111.320135
  91. Zullo AJ, Jurcic Smith KL, Lee S. Mammalian target of Rapamycin inhibition and mycobacterial survival are uncoupled in murine macrophages. BMC Biochem 2014;15:4.
  92. Pohl K, Grimm XA, Caceres SM, Poch KR, Rysavy N, Saavedra M, Nick JA, Malcolm KC. Mycobacterium abscessus clearance by neutrophils is independent of autophagy. Infect Immun 2020;88:e00024-20.
  93. Sohn H, Kim HJ, Kim JM, Kwon OJ, Koh WJ, Shin SJ. High virulent clinical isolates of Mycobacterium abscessus from patients with the upper lobe fibrocavitary form of pulmonary disease. Microb Pathog 2009;47:321-328. https://doi.org/10.1016/j.micpath.2009.09.010
  94. Kim SW, Subhadra B, Whang J, Back YW, Bae HS, Kim HJ, Choi CH. Clinical Mycobacterium abscessus strain inhibits autophagy flux and promotes its growth in murine macrophages. Pathog Dis 2017;75:ftx107.
  95. Junkins RD, McCormick C, Lin TJ. The emerging potential of autophagy-based therapies in the treatment of cystic fibrosis lung infections. Autophagy 2014;10:538-547. https://doi.org/10.4161/auto.27750
  96. Gaudino SJ, Kumar P. Cross-talk between antigen presenting cells and T cells impacts intestinal homeostasis, bacterial infections, and tumorigenesis. Front Immunol 2019;10:360.
  97. Munroe ME, Bishop GA. A costimulatory function for T cell CD40. J Immunol 2007;178:671-682. https://doi.org/10.4049/jimmunol.178.2.671
  98. Philips EA, Techova AS, Mor A, Kong X. Structural, functional, and evolutionary differences between PD-L1 and PD-L2. J Immunol 2018;200.
  99. Wu UI, Olivier KN, Kuhns DB, Fink DL, Sampaio EP, Zelazny AM, Shallom SJ, Marciano BE, Lionakis MS, Holland SM. Patients with idiopathic pulmonary nontuberculous mycobacterial disease have normal Th1/Th2 cytokine responses but diminished Th17 cytokine and enhanced granulocyte-macrophage colony-stimulating factor production. Open Forum Infect Dis 2019;6:ofz484.
  100. Lim A, Allison C, Price P, Waterer G. Susceptibility to pulmonary disease due to Mycobacterium avium-intracellulare complex may reflect low IL-17 and high IL-10 responses rather than Th1 deficiency. Clin Immunol 2010;137:296-302. https://doi.org/10.1016/j.clim.2010.07.011
  101. Abate G, Hamzabegovic F, Eickhoff CS, Hoft DF. BCG vaccination induces M. avium and M. abscessus cross-protective immunity. Front Immunol 2019;10:234.
  102. Shu CC, Pan SW, Feng JY, Wang JY, Chan YJ, Yu CJ, Su WJ. The clinical significance of programmed death-1, regulatory T cells and myeloid derived suppressor cells in patients with nontuberculous mycobacteria-lung disease. J Clin Med 2019;8:736.
  103. Gibson RL, Burns JL, Ramsey BW. Pathophysiology and management of pulmonary infections in cystic fibrosis. Am J Respir Crit Care Med 2003;168:918-951. https://doi.org/10.1164/rccm.200304-505SO
  104. Monin L, Mehta S, Elsegeiny W, Gopal R, McAleer JP, Oury TD, Kolls J, Khader SA. Aspergillus fumigatus preexposure worsens pathology and improves control of Mycobacterium abscessus pulmonary infection in mice. Infect Immun 2018;86:e00859-17.
  105. Lutzky VP, Ratnatunga CN, Smith DJ, Kupz A, Doolan DL, Reid DW, Thomson RM, Bell SC, Miles JJ. Anomalies in T cell function are associated with individuals at risk of Mycobacterium abscessus complex infection. Front Immunol 2018;9:1319.
  106. Storder J, Renard P, Arnould T. Update on the role of Sirtuin 3 in cell differentiation: a major metabolic target that can be pharmacologically controlled. Biochem Pharmacol 2019;169:113621.
  107. Marcus JM, Andrabi SA. SIRT3 regulation under cellular stress: making sense of the ups and downs. Front Neurosci 2018;12:799.
  108. Mirza AZ, Althagafi II, Shamshad H. Role of PPAR receptor in different diseases and their ligands: physiological importance and clinical implications. Eur J Med Chem 2019;166:502-513. https://doi.org/10.1016/j.ejmech.2019.01.067
  109. Kim YS, Kim JK, Hanh BT, Kim SY, Kim HJ, Kim YJ, Jeon SM, Park CR, Oh GT, Park JW, et al. The peroxisome proliferator-activated receptor alpha- agonist gemfibrozil promotes defense against Mycobacterium abscessus infections. Cells 2020;9:648.
  110. Gonzalez-Mancera MS, Johnson B, Mirsaeidi M. STAT3 gain-of-function mutation in a patient with pulmonary Mycobacterium abscessus infection. Respir Med Case Rep 2020;30:101125.
  111. Wang X, Chen S, Ren H, Chen J, Li J, Wang Y, Hua Y, Wang X, Huang N. HMGN2 regulates nontuberculous mycobacteria survival via modulation of M1 macrophage polarization. J Cell Mol Med 2019;23:7985-7998. https://doi.org/10.1111/jcmm.14599
  112. O'Neill LA, Sheedy FJ, McCoy CE. MicroRNAs: the fine-tuners of Toll-like receptor signalling. Nat Rev Immunol 2011;11:163-175. https://doi.org/10.1038/nri2957
  113. Silwal P, Kim YS, Basu J, Jo EK. The roles of microRNAs in regulation of autophagy during bacterial infection. Semin Cell Dev Bio 2020;101:51-58. https://doi.org/10.1016/j.semcdb.2019.07.011
  114. Kim HJ, Kim IS, Lee SG, Kim YJ, Silwal P, Kim JY, Kim JK, Seo W, Chung C, Cho HK, et al. MiR-144-3p is associated with pathological inflammation in patients infected with Mycobacteroides abscessus. Exp Mol Med 2021;53:136-149. https://doi.org/10.1038/s12276-020-00552-0
  115. Han SA, Jhun BW, Kim SY, Moon SM, Yang B, Kwon OJ, Daley CL, Shin SJ, Koh WJ. miRNA expression profiles and potential as biomarkers in nontuberculous mycobacterial pulmonary disease. Sci Rep 2020;10:3178.