Mucosal-associated invariant T cells: new players in CF lung disease?

  • Nidhi AnilEmail author


The past decade has witnessed a surge in research centered around exploring the role of the enigmatic innate immune-like lymphocyte MAIT cell in human disease. Recent evidence has led to the elucidation of its role as a potent defender at mucosal surfaces including lungs due to its capacity to mount a formidable immediate response to bacterial pathogens. MAIT cells have a unique attribute of recognizing microbial ligands in conjunction with non-classical MHC-related protein MR1. Recent studies have demonstrated their contribution in the pathogenesis of chronic pulmonary disorders including asthma and chronic obstructive pulmonary disease. Several cellular players including innate immune cells are active contributors in the immune imbalance present in cystic fibrosis(CF) lung. This immune dysregulation serves as a central pivot in disease pathogenesis, responsible for causing immense structural damage in the CF lung. The present review focuses on understanding the role of MAIT cells in CF lung disease. Future studies directed at understanding the possible relationship between MAIT cells and regulatory T cells (Tregs) in CF lung disease could unravel a holistic picture where a combination of antimicrobial effects of MAIT cells and anti-inflammatory effects of Tregs could be exploited in synergy to alleviate the rapid deterioration of lung function in CF lung disease due to the underlying complex interplay between persistent infection and inflammation.


Cystic fibrosis Pulmonary inflammation MAIT cells 



  1. 1.
    Davis PB, Drumn M, Konstan MW. Cystic fibrosis state of art. Am J Respir Crit Care Med. 1996;154:1229–56.CrossRefGoogle Scholar
  2. 2.
    Nichols DP, Chmiel JF. Inflammation and its genesis in cystic fibrosis. Pediatr Pulmonol. 2015;50:539–56.CrossRefGoogle Scholar
  3. 3.
    Bruscia EM, Bonfield TL. Innate and adaptive immunity in cystic fibrosis. Clin Chest Med. 2016;37:17–29.CrossRefGoogle Scholar
  4. 4.
    Moss RB, Hsu YP, Old L. Cytokine dysregulation in activated cystic fibrosis (CF) peripheral lymphocytes. Clin Exp Immunol. 2000;120:518–25.CrossRefGoogle Scholar
  5. 5.
    Dubin PJ, Mc Allister F, Kolls JK. Is cystic fibrosis a Th 17 disease? Inflamm Res. 2001;56:221–7.CrossRefGoogle Scholar
  6. 6.
    Cantin AM, Hartl D, Konstan MW, Chmiel JF. Inflammation in cystic fibrosis lung disease Pathogenesis and therapy. J Cyst Fibros. 2015;14:419–30.CrossRefGoogle Scholar
  7. 7.
    Martin E, Triener E, Duban L, Guerri L, Laude H, Toly C, Premel V, Devys A, Moura IC, Tilloy F, Cherif S, Vera G, Latour S, Soudais C, Lantz O. Stepwise development of MAIT Cells in mouse and humans. PLOS Biol. 2009;7:e54.CrossRefGoogle Scholar
  8. 8.
    Tilloy F, Triener E, Park SH, Gracia C, Lemonnier F, de la Salle H, Bendelac A, Bonneville M, Lantzo AP. An invariant T cell receptor alpha chain defines a novel TAP independent mayor histocompatibility complex 1b alpha/beta restricted sub population in mammals. J Exp Med. 1999;189:1907–21.CrossRefGoogle Scholar
  9. 9.
    Leeansyah E, Loh L, Nixon DF, Sanberg JK. Acquisition of innate like microbial reactivity in mucosal tissues during fetal MAIT cell development. Nat Commun. 2014;5:3413.CrossRefGoogle Scholar
  10. 10.
    Napler RJ, Adams EJ, Gold MC, Lewinsohn DM. The role of mucosal associated invariant T cells in antimicrobial immunity. Front Immunol. 2015;6:344.Google Scholar
  11. 11.
    Reantragoon R, Corbett AJ, Sakala IG, Gheravdin NA, Furness JB, Chen Z, et al. Antigen loaded MR1 tetramers define T cell receptor heterogeneity in mucosal associated invariant T cell. J Exp Med. 2013;210:2305–20.CrossRefGoogle Scholar
  12. 12.
    Lepore M, Kalincenko A, Colone A, Paleja B, Singhal A, Tschumi A, et al. Parallel T cell cloning and deep sequencing of human MAIT cell reveal stable oligoclonal TCRβ repertoire. Nat Commun. 2014;5:3866.CrossRefGoogle Scholar
  13. 13.
    Gold MC, Ehlinger HD, Cook MS, Symk-Pearson SK, Wille PT, Ungerleider RM, et al. Human innate immune mycobacterium tuberculosis reactive alpha beta TCR + thymocytes. Plos Pathogen. 2008;4:39.CrossRefGoogle Scholar
  14. 14.
    Gold MC, Eid T, Symk-Pearson S, Eberling Y, Swarbrick GM, Langley SM, et al. Human thymic MR1-restricted MAIT cells are innate pathogen reactive effectors that adapt following thymus egress. Mucosal Immunol. 2013;6:35–44.CrossRefGoogle Scholar
  15. 15.
    Godfrey DL, Uldrich AP, Mc Chuskey I, Roosjulin J, Moody DR. The burgeoning family of unconventional T cell. Nat Immunol. 2015;10:1114–23.CrossRefGoogle Scholar
  16. 16.
    Treiner E, Duban L, Bahram S, Radosavljevic M, Wanner V, Tilloy E, et al. Selection of evolutionarily conserved mucosal associated invariant T cells by MR1. Nature. 2003;422:164–9.CrossRefGoogle Scholar
  17. 17.
    Huang S, Gilfillan S, Cella M, Miley MJ, Lantz O, Lybarger L, et al. Evidence of MRI antigen presentation to mucosal associated invariant T cells. J Biol Chem. 2005;280:183–93.CrossRefGoogle Scholar
  18. 18.
    Kjer-Nielsen I, Patel O, Corbett AI, Le Nours J, Meehan B, Liu L, et al. MR1 presents microbial vitamin B metabolites to MAIT cells. Nature. 2012;49:717–23.CrossRefGoogle Scholar
  19. 19.
    Patel O, Kjer-Nielsen I, LeNours J, Eckle SB, Birikinshaw R, Beddoe T, Corbett AJ, et al. Recognition of vitamin B metabolites by mucosal invariant T Cells. Nat Commun. 2013;4:2142.CrossRefGoogle Scholar
  20. 20.
    Gold MC, Cerri S, Symk-Pearson S, Cansler ME, Voyt TM, Delepine J, Winata E, et al. Human mucosal associated invariant T cells detect bacterially infected cells. PLoS Biol. 2010;8:e1000407.CrossRefGoogle Scholar
  21. 21.
    Meermeier EW, Harriff MJ, Karamooz E, Lewinsohn DM. MAIT cells and microbial immunity. Immunol Cell Biol. 2018. Scholar
  22. 22.
    Corbett AJ, Eckle SB, Birkinshaw RW, Liu L, Patel B, Mahony J, et al. T cell activation by transitory neo antigens derived from distinct microbial pathways. Nature. 2014;509:361–5.CrossRefGoogle Scholar
  23. 23.
    Greene JM, Dash P, Roy S, McMurtrey C, Awad W, Reed JS, Hammond KR, Abdulhagg S, Wu HL, Burwitz BJ. MRI restricted mucosal associated invariant T (MAIT) cell respond to myobacterial vaccination and infection in non human primates. Mucosal Immunol. 2017;10:802.CrossRefGoogle Scholar
  24. 24.
    Ussher JE, Bilton M, Attwood E, Shadwell S, Richardson R, de Lara C, et al. CD161+ CD8+ T cells including MAIT cell subsets are specifically activated by IL12+IL18 in a TCR independent manner. Eur J Immunol. 2014;44:195–203.CrossRefGoogle Scholar
  25. 25.
    Sattler A, Dang Heine C, Reinke P, Babel N. IL-15 dependent induction of IL-18 secretion as a feedback mechanism controlling human MAIT cell effector functions. Eur J Immunol. 2015;45:2286–98.CrossRefGoogle Scholar
  26. 26.
    Lambrecht BN, Hammad JH. The immunology of asthma. Nat Immunol. 2015;16:45–56.CrossRefGoogle Scholar
  27. 27.
    Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med. 2012;18:716–25.CrossRefGoogle Scholar
  28. 28.
    Hinks TS, Zhou X, Staples KJ, Dimitrov B, Manta A, Petrossian T, et al. Innate and adaptive T cells in asthmatic patients: relationship to severity and disease mechanisms. J Allergy Clin Immunol. 2015;136:323–33.CrossRefGoogle Scholar
  29. 29.
    Lee OJ, Cho YN, Kee SJ, Kim MJ, Jin HM, Lee SJ, et al. Circulating mucosal associated invariant T cell levels and their cytokine levels in healthy adults. Exp Gerontol. 2014;49:49–54.CrossRefGoogle Scholar
  30. 30.
    Lezmi G, Abou Tam R, Dietrich C, Chatenoud L, De Blic J, Leite Demoraes M. Circulating IL-17 producing mucosal associated invariant T cells (MAIT) are associated with asthma. Clin Immunol. 2018;188:7–11.CrossRefGoogle Scholar
  31. 31.
    Chandra S, Wingender G, Greenbacum JA, Khurana A, Gholami AM, Ganesan AP, et al. Development of asthma in inner city children possible roles of MAIT cells and variation in the home environment. J Immunol. 2018;200:1995–2003.CrossRefGoogle Scholar
  32. 32.
    Hinks TSC, Wallington JC, Williams AP, Djukanovic R, Staples KJ, Wilkinson TMA. Steroid induced deficiency of Mucosal -associated invariant T cells in chronic obstructive pulmonary disease lung implications for non typeable Haemophilis influenzae infection. Am J Respir Crit Care Med. 2015;194:1208–18.CrossRefGoogle Scholar
  33. 33.
    Kwon YS, Jin HM, Cho YN, Kin MJ, Kang JH, Jung HJ, Park KJ, Kee HJ, Kee SJ, Park YW. Mucosal associated invariant T cell deficiency in chronic obstructive pulmonary disease. COPD. 2016;13:196–202.CrossRefGoogle Scholar
  34. 34.
    Szabo M, Sarasi V, Baliko Z, Bodo K, Farkas N, Berki T, Engelman P. Deficiency of innate like T lymphocytes in chronic obstructive pulmonary disease. Respir Res. 2017;18:197.CrossRefGoogle Scholar
  35. 35.
    Ussher JE, Klenerman P, Willberg CB. Mucosal associated invariant T cells, new players in anti-bacterial immunity. Front Immunol. 2014;5:450.CrossRefGoogle Scholar
  36. 36.
    Wong EB, Ndungu T, Kasprowicz VO. The role of mucosal associated invariant T Cells in infectious diseases. Immunol. 2016;150:45–54.CrossRefGoogle Scholar
  37. 37.
    Kumar V, Ahmad A. Role of MAIT cells in immunopathogenesis of inflammatory diseases: new players in old game. Int Rev Immunol. 2018;37:90–110.CrossRefGoogle Scholar
  38. 38.
    Le Bourhis L, Dusseaux M, Bohineust A, Bessoles E, Martin E, Prenel V, et al. MAIT cells detect and efficiently life bacterially infected epithelial cells. PLoS Pathog. 2013;9:e1003681.CrossRefGoogle Scholar
  39. 39.
    Chau WJ, Trus-Cott SM, Eickhoff CS, Blazevic A, Hoft DF, Hausen TH. Polyclonal mucosa associated invariant T cells have unique innate functions in bactrerial infection. Infect Immun. 2012;80:3256–67.CrossRefGoogle Scholar
  40. 40.
    Jiang J, Yang B, An H, Wang X, Liu Y, Cao Z, Zhai F, et al. Mucosal associated invariant T cells from patients with tuberculosis exhibit impaired immune response. J Infect. 2016;72:338–52.CrossRefGoogle Scholar
  41. 41.
    Ruimy CM, Yousef GB, Lambert M, Tourret M, Ghazarian L, Faye A, Zucmann SC, Veronique H. Mucosal associated invariant T cells levels are reduced in peripheral blood and lungs of children with active pulmonary tuberculosis. Front Immunol. 2019;10:206.CrossRefGoogle Scholar
  42. 42.
    Georgel P, Radosavljevic M, Macquin C, Bahram S. The non conventional MHC class I MR1 molecule controls infection by Klebsiella pneumoniae in mice. Mol Immunol. 2011;48:769–75.CrossRefGoogle Scholar
  43. 43.
    Meirovics A, Yankelevich WJ, Cowley SC. MAIT cells are critical for optimal mucosal immune responses during in vivo pulmonary bacterial infection. Proc Natl Acad Sci USA. 2013;110:e3119–28.CrossRefGoogle Scholar
  44. 44.
    Hartmann N, Harriff MJ, McMurtrey CP, Hilderbrand WH, Lewinsohn DM, Kronenberg M. Role of MAIT cells in pulmonary bacterial infection. Mol Immunol. 2018;101:155–9.CrossRefGoogle Scholar
  45. 45.
    Smith DJ, Hill GR, Bell SC, Reid DW. Reduced mucosal associated invariant T cells are associated with increased disease severity and Pseudomonas aeruginosa infection in cystic fibrosis. PLoS One. 2014;9:e109891.CrossRefGoogle Scholar
  46. 46.
    Pincikova T, Paquin Proulx D, Moll M, Flodstrom-Tulberg M, Hjelte L, Sandberg JK. Severely impaired control of bacterial infections in a patient with cystic fibrosis defective in mucosal associated invariant T cells. Chest. 2018;153:e93–6.CrossRefGoogle Scholar
  47. 47.
    Pincikova T, Paquin- Proulx D, Sandberg M, Flodstrom T, Hjete L. Vitamin D treatment modulates immune activation in cystic fibrosis. Clin Exp Immunol. 2017;189:359–71.CrossRefGoogle Scholar
  48. 48.
    McGuire JK. Regulatory T cells in cystic fibrosis lung disease. More answers, more questions. Am J Respir Crit Care Med. 2015;19:866–8.CrossRefGoogle Scholar
  49. 49.
    Anil N, Singh M. CD4+ CD25 (high) FOXP3+ regulatory T cells correlate with FEV1 in north Indian children with cystic fibrosis. Immunol Invest. 2014;43:535–43.CrossRefGoogle Scholar
  50. 50.
    Hector A, Schafer H, Poschel S, Fischer A, Fritzsching B, Rathan A, et al. Regulatory T cell impairment in cystic fibrosis patients with chronic pseudomonas infection. Am J Respir Crit Care Med. 2015;191:914–23.CrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Centre For Stem Cell Tissue Engineering and Biomedical ExcellencePanjab UniversityChandigarhIndia

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