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Applied Microbiology and Biotechnology

, Volume 102, Issue 10, pp 4339–4343 | Cite as

Duox2-induced innate immune responses in the respiratory epithelium and intranasal delivery of Duox2 DNA using polymer that mediates immunization

  • Yung Jin Jeon
  • Hyun Jik Kim
Mini-Review

Abstract

Respiratory mucosa especially nasal epithelium is well known as the first-line barrier of air-borne pathogens. High levels of reactive oxygen species (ROS) are detected in in vitro cultured human epithelial cells and in vivo lung. With identification of NADPH oxidase (Nox) system of respiratory epithelium, the antimicrobial role of ROS has been studied. Duox2 is the most abundant Nox isoform and produces the regulated amount of ROS in respiratory epithelium. Duox2-derived ROS are involved in antiviral innate immune responses but more studies are needed to verify the mechanism. In respiratory epithelium, Duox2-derived ROS is critical for recognition of virus through families retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5) at the early stage of antiviral innate immune responses. Various secreted interferons (IFNs) play essential roles for antiviral host defense by downstream cell signaling, and transcription of IFN-stimulated genes is started to suppress viral replication. Type I and type III IFNs are verified more responsible for influenza A virus (IAV) infection in respiratory epithelium and Duox2 is required to regulate IFN-related immune responses. Transient overexpression of Duox2 using cationic polymer polyethylenimine (PEI) induces secretion of type I and type III IFNs and significantly attenuated IAV replication in respiratory epithelium. Here, we discuss Duox2-mediated antiviral innate immune responses and the role of Duox2 as a mucosal vaccine to resist respiratory viral infection.

Keywords

Duox2 Cationic polymer Reactive oxygen species Influenza A virus Respiratory epithelium 

Notes

Author contributions

Y.J.J. and H.J.K. conceived the study and designed the experimental plan. Y.J.J. carried out a major portion of the study including data collection and H.J.K. drafted the manuscript.

Funding information

This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, (2016R1D1A1B01014116) (H.J.K.), a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI15C2923) (H.J.K.), and a grant from the Korea Healthcare Technology R&D Project of the Ministry for Health, Welfare, and Family Affairs (HI15C0694) (H.J.K.).

Compliance with ethical standards

Competing interests

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors. The Institutional Review Board of the Seoul National University College of Medicine approved all experiments (IACUC number 15-0263) and the data collection was carried out in accordance with the approved guidelines.

References

  1. Ameziane-El-Hassani R, Morand S, Boucher JL, Frapart YM, Apostolou D, Agnandji D, Gnidehou S, Ohayon R, Noel-Hudson MS, Francon J, Lalaoui K, Virion A, Dupuy C (2005) Dual oxidase-2 has an intrinsic Ca2+-dependent H2O2-generating activity. J Biol Chem 280(34):30046–30054.  https://doi.org/10.1074/jbc.M500516200 CrossRefPubMedGoogle Scholar
  2. Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408(6809):239–247.  https://doi.org/10.1038/35041687 CrossRefPubMedGoogle Scholar
  3. Fischer H (2009) Mechanisms and function of DUOX in epithelia of the lung. Antioxid Redox Signal 11(10):2453–2465.  https://doi.org/10.1089/ARS.2009.2558 CrossRefPubMedPubMedCentralGoogle Scholar
  4. Forteza R, Salathe M, Miot F, Forteza R, Conner GE (2005) Regulated hydrogen peroxide production by Duox in human airway epithelial cells. Am J Respir Cell Mol Biol 32(5):462–469.  https://doi.org/10.1165/rcmb.2004-0302OC CrossRefPubMedGoogle Scholar
  5. Garcia-Sastre A, Biron CA (2006) Type 1 interferons and the virus-host relationship: a lesson in detente. Science 312(5775):879–882.  https://doi.org/10.1126/science.1125676 CrossRefPubMedGoogle Scholar
  6. Geiszt M, Witta J, Baffi J, Lekstrom K, Leto TL (2003) Dual oxidases represent novel hydrogen peroxide sources supporting mucosal surface host defense. FASEB J 17(11):1502–1504.  https://doi.org/10.1096/fj.02-1104fje CrossRefPubMedGoogle Scholar
  7. Gitlin L, Benoit L, Song C, Cella M, Gilfillan S, Holtzman MJ, Colonna M (2010) Melanoma differentiation-associated gene 5 (MDA5) is involved in the innate immune response to Paramyxoviridae infection in vivo. PLoS Pathog 6(1):e1000734.  https://doi.org/10.1371/journal.ppat.1000734 CrossRefPubMedPubMedCentralGoogle Scholar
  8. Harper RW, Xu C, Eiserich JP, Chen Y, Kao CY, Thai P, Setiadi H, Wu R (2005) Differential regulation of dual NADPH oxidases/peroxidases, Duox1 and Duox2, by Th1 and Th2 cytokines in respiratory tract epithelium. FEBS Lett 579(21):4911–4917.  https://doi.org/10.1016/j.febslet.2005.08.002 CrossRefPubMedGoogle Scholar
  9. Hong SN, Kim JY, Kim H, Kim DY, Won TB, Han DH, Rhee CS, Kim HJ (2016) Duox2 is required for the transcription of pattern recognition receptors in acute viral lung infection: an interferon-independent regulatory mechanism. Antivir Res 134:1–5.  https://doi.org/10.1016/j.antiviral.2016.08.017 CrossRefPubMedGoogle Scholar
  10. Horimoto T, Kawaoka Y (2005) Influenza: lessons from past pandemics, warnings from current incidents. Nat Rev Microbiol 3(8):591–600.  https://doi.org/10.1038/nrmicro1208 CrossRefPubMedGoogle Scholar
  11. Joo JH, Ryu JH, Kim CH, Kim HJ, Suh MS, Kim JO, Chung SY, Lee SN, Kim HM, Bae YS, Yoon JH (2012) Dual oxidase 2 is essential for the toll-like receptor 5-mediated inflammatory response in airway mucosa. Antioxid Redox Signal 16(1):57–70.  https://doi.org/10.1089/ars.2011.3898 CrossRefPubMedGoogle Scholar
  12. Kawai T, Akira S (2006) Innate immune recognition of viral infection. Nat Immunol 7(2):131–137.  https://doi.org/10.1038/ni1303 CrossRefPubMedGoogle Scholar
  13. Kim BJ, Cho SW, Jeon YJ, An S, Jo A, Lim JH, Kim DY, Won TB, Han DH, Rhee CS, Kim HJ (2017) Intranasal delivery of Duox2 DNA using cationic polymer can prevent acute influenza A viral infection in vivo lung. Appl Microbiol Biotechnol 102:105–115.  https://doi.org/10.1007/s00253-017-8512-1 CrossRefPubMedGoogle Scholar
  14. Kim HJ, Kim CH, Kim MJ, Ryu JH, Seong SY, Kim S, Lim SJ, Holtzman MJ, Yoon JH (2015) The induction of pattern-recognition receptor expression against influenza a virus through Duox2-derived reactive oxygen species in nasal mucosa. Am J Respir Cell Mol Biol 53(4):525–535.  https://doi.org/10.1165/rcmb.2014-0334OC CrossRefPubMedPubMedCentralGoogle Scholar
  15. Kim HJ, Kim CH, Ryu JH, Joo JH, Lee SN, Kim MJ, Lee JG, Bae YS, Yoon JH (2011) Crosstalk between platelet-derived growth factor-induced Nox4 activation and MUC8 gene overexpression in human airway epithelial cells. Free Radic Biol Med 50(9):1039–1052.  https://doi.org/10.1016/j.freeradbiomed.2011.01.014 CrossRefPubMedGoogle Scholar
  16. Kim HJ, Kim CH, Ryu JH, Kim MJ, Park CY, Lee JM, Holtzman MJ, Yoon JH (2013) Reactive oxygen species induce antiviral innate immune response through IFN-lambda regulation in human nasal epithelial cells. Am J Respir Cell Mol Biol 49(5):855–865.  https://doi.org/10.1165/rcmb.2013-0003OC CrossRefPubMedPubMedCentralGoogle Scholar
  17. Kim HJ, Park YD, Moon UY, Kim JH, Jeon JH, Lee JG, Bae YS, Yoon JH (2008) The role of Nox4 in oxidative stress-induced MUC5AC overexpression in human airway epithelial cells. Am J Respir Cell Mol Biol 39(5):598–609.  https://doi.org/10.1165/rcmb.2007-0262OC CrossRefPubMedGoogle Scholar
  18. Koltsida O, Hausding M, Stavropoulos A, Koch S, Tzelepis G, Ubel C, Kotenko SV, Sideras P, Lehr HA, Tepe M, Klucher KM, Doyle SE, Neurath MF, Finotto S, Andreakos E (2011) IL-28A (IFN-lambda2) modulates lung DC function to promote Th1 immune skewing and suppress allergic airway disease. EMBO Mol Med 3(6):348–361.  https://doi.org/10.1002/emmm.201100142 CrossRefPubMedPubMedCentralGoogle Scholar
  19. Levy DE, Darnell JE Jr (2002) Stats: transcriptional control and biological impact. Nat Rev Mol Cell Biol 3(9):651–662.  https://doi.org/10.1038/nrm909 CrossRefPubMedGoogle Scholar
  20. Liu T, Castro S, Brasier AR, Jamaluddin M, Garofalo RP, Casola A (2004) Reactive oxygen species mediate virus-induced STAT activation: role of tyrosine phosphatases. J Biol Chem 279(4):2461–2469.  https://doi.org/10.1074/jbc.M307251200 CrossRefPubMedGoogle Scholar
  21. Nose O, Harada T, Miyai K, Hata N, Ogawa M, Maki I, Kanaya S, Kimura S, Shimizu K, Yabuuchi H (1986) Transient neonatal hypothyroidism probably related to immaturity of thyroidal iodine organification. J Pediatr 108(4):573–576CrossRefPubMedGoogle Scholar
  22. Rhee SG (2006) Cell signaling. H2O2, a necessary evil for cell signaling. Science 312(5782):1882–1883.  https://doi.org/10.1126/science.1130481 CrossRefPubMedGoogle Scholar
  23. Schwarzer C, Machen TE, Illek B, Fischer H (2004) NADPH oxidase-dependent acid production in airway epithelial cells. J Biol Chem 279(35):36454–36461.  https://doi.org/10.1074/jbc.M404983200 CrossRefPubMedGoogle Scholar
  24. Shao MX, Nadel JA (2005) Dual oxidase 1-dependent MUC5AC mucin expression in cultured human airway epithelial cells. Proc Natl Acad Sci U S A 102(3):767–772.  https://doi.org/10.1073/pnas.0408932102 CrossRefPubMedPubMedCentralGoogle Scholar
  25. Snelgrove RJ, Edwards L, Rae AJ, Hussell T (2006) An absence of reactive oxygen species improves the resolution of lung influenza infection. Eur J Immunol 36(6):1364–1373.  https://doi.org/10.1002/eji.200635977 CrossRefPubMedGoogle Scholar
  26. Strengert M, Jennings R, Davanture S, Hayes P, Gabriel G, Knaus UG (2014) Mucosal reactive oxygen species are required for antiviral response: role of Duox in influenza a virus infection. Antioxid Redox Signal 20(17):2695–2709.  https://doi.org/10.1089/ars.2013.5353 CrossRefPubMedGoogle Scholar
  27. van der Vliet A (2008) NADPH oxidases in lung biology and pathology: host defense enzymes, and more. Free Radic Biol Med 44(6):938–955.  https://doi.org/10.1016/j.freeradbiomed.2007.11.016 CrossRefPubMedGoogle Scholar
  28. Wesley UV, Bove PF, Hristova M, McCarthy S, van der Vliet A (2007) Airway epithelial cell migration and wound repair by ATP-mediated activation of dual oxidase 1. J Biol Chem 282(5):3213–3220.  https://doi.org/10.1074/jbc.M606533200 CrossRefPubMedGoogle Scholar
  29. Wu S, Metcalf JP, Wu W (2011) Innate immune response to influenza virus. Curr Opin Infect Dis 24(3):235–240.  https://doi.org/10.1097/QCO.0b013e328344c0e3 CrossRefPubMedGoogle Scholar
  30. Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, Taira K, Akira S, Fujita T (2004) The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol 5(7):730–737.  https://doi.org/10.1038/ni1087 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Otorhinolaryngology-Head and Neck SurgerySeoul National University Hospital, Seoul National University College of MedicineSeoulSouth Korea

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