Basic Science Article | Published:

Pseudomonas aeruginosa-derived exosomes ameliorates allergic reactions via inducing the Treg response in asthma

Pediatric Researchvolume 84pages125133 (2018) | Download Citation

Subjects

Abstract

Background

Exosomes are nanovesicles originating from multivesicular bodies that have complex functions and significant therapeutic effects in many diseases. In the present study, we successfully extracted exosomes from Pseudomonas aeruginosa and assessed the effect of those exosomes on the development of the allergic response in two types of classic asthma models.

Methods

Female BALB/c mice were administrated with P. aeruginosa-derived exosomes 1 week before ovalbumin (OVA) or house dust mite (HDM) sensitization. Bronchoalveolar lavage fluid, serums and lung tissues were collected and analyzed for pathophysiology and immune responses.

Results

Our results demonstrated that P. aeruginosa-derived exosomes inhibited the development of airway hyper-responsiveness (AHR), peribronchial and perivascular inflammation in lung tissues and the level of serum IgE. Moreover, this protective effect was associated with an increase in the regulatory T cell (Treg) response and a concomitant decreased Th2 response.

Conclusions

In conclusion, these observations demonstrated that P. aeruginosa-derived exosomes could induce protection against allergic sensitization in asthma mice, and our study provided a new insight to prevent allergic diseases.

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References

  1. 1.

    Clark, N. M. Community-based approaches to controlling childhood asthma. Annu. Rev. Public Health 33, 193–208 (2012).

  2. 2.

    Wenzel, S. E. & Busse, W. W. Severe asthma: lessons from the Severe Asthma Research Program. J. Allergy Clin. Immunol. 119, 14–21 (2007).

  3. 3.

    Lötvall, J. et al. Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J. Allergy Clin. Immunol. 127, 355–360 (2011).

  4. 4.

    Mazzarella, G., Bianco, A., Catena, E., De Palma, R. & Abbate, G. F. Th1/Th2 lymphocyte polarization in asthma. Allergy 55, 6–9 (2000). Suppl 61.

  5. 5.

    Ray, A., Khare, A., Krishnamoorthy, N., Qi, Z. & Ray, P. Regulatory T cells in many flavors control asthma. Mucosal Immunol. 3, 216–229 (2010).

  6. 6.

    Hartl, D. et al. Quantitative and functional impairment of pulmonary CD4+ CD25hi regulatory T cells in pediatric asthma. J. Allergy Clin. Immunol. 119, 1258–1266 (2007).

  7. 7.

    Robbins, P. D. & Morelli, A. E. Regulation of immune responses by extracellular vesicles. Nat. Rev. Immunol. 14, 195–208 (2014).

  8. 8.

    Chutkan, H., Macdonald, I., Manning, A. & Kuehn, M. J. Quantitative and qualitative preparations of bacterial outer membrane vesicles. Methods Mol. Biol. 966, 259–272 (2013).

  9. 9.

    Hough, K. P., Chanda, D., Duncan, S. R., Thannickal, V. J. & Deshane, J. S. Exosomes in immunoregulation of chronic lung diseases. Allergy 72, 534–544 (2017).

  10. 10.

    Okoye, I. S. et al. MicroRNA-containing T-regulatory-cell-derived exosomes suppress pathogenic T helper 1 cells. Immunity 41, 89–103 (2014).

  11. 11.

    Wakkach, A. et al. Characterization of dendritic cells that induce tolerance and T regulatory 1 cell differentiation in vivo. Immunity 18, 605–617 (2003).

  12. 12.

    Mutwiri, G., van Drunen Littel-van den Hurk, S. & Babiuk, L. A. Approaches to enhancing immune responses stimulated by CpG oligodeoxynucleotides. Adv. Drug. Deliv. Rev. 61, 226–232 (2009).

  13. 13.

    Schuijs, M. J. et al. Farm dust and endotoxin protect against allergy through A20 induction in lung epithelial cells. Science 349, 1106–1110 (2015).

  14. 14.

    Stein, M. M. et al. Innate immunity and asthma risk in Amish And Hutterite farm children. N. Engl. J. Med. 375, 411–421 (2016).

  15. 15.

    Vanaja, S. K. et al. Bacterial outer membrane vesicles mediate cytosolic localization of LPS and Caspase-11 Activation. Cell 165, 1106–1119 (2016).

  16. 16.

    Choi, D. S. et al. Proteomic analysis of outer membrane vesicles derived from Pseudomonas aeruginosa. Proteomics 11, 3424–3429 (2011).

  17. 17.

    Chałupniak, A. et al. Application of quartz tuning forks for detection of endotoxins and Gram-negative bacterial cells by monitoring of Limulus Amebocyte Lysate coagulation. Biosens. Bioelectron 58, 132–137 (2014).

  18. 18.

    Niu, C. et al. Vitamin A maintains the airway epithelium in a murine model of asthma by suppressing glucocorticoid-induced leucine zipper. Clin. Exp. Allergy 46, 848–860 (2016).

  19. 19.

    Johnson, J. R. et al. Divergent immune responses to house dust mite lead to distinct structural-functional phenotypes. Am. J. Physiol. Lung. Cell Mol. Physiol. 293, L730–L739 (2007).

  20. 20.

    Théry, C., Amigorena, S., Raposo, G. & Clayton, A. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr. Protoc. Cell. Biol. 3, 22 (2006).

  21. 21.

    Valadi, H. et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 9, 654–659 (2007).

  22. 22.

    Kamerkar, S. et al. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Nature 546, 498–503 (2017).

  23. 23.

    Sharma, R., Huang, X., Brekken, R. A. & Schroit, A. J. Detection of phosphatidylserine-positive exosomes for the diagnosis of early-stage malignancies. Br. J. Cancer 117, 545–552 (2017).

  24. 24.

    Khan, M. et al. Embryonic stem cell-derived exosomes promote endogenous repair mechanisms and enhance cardiac function following myocardial infarction. Circ. Res. 117, 52–64 (2015).

  25. 25.

    Ho, D. H., Yi, S., Seo, H., Son, I. & Seol, W. Increased DJ-1 in urine exosome of Korean males with Parkinson’s disease. Biomed. Res. Int. 2014, 704678 (2014).

  26. 26.

    Admyre, C. et al. Exosomes - nanovesicles with possible roles in allergic inflammation. Allergy 63, 404–408 (2008).

  27. 27.

    Van Niel, G. et al. Intestinal epithelial exosomes carry MHC class II/peptides able to inform the immune system in mice. Gut 52, 1690–1697 (2003).

  28. 28.

    Admyre, C. et al. B cell-derived exosomes can present allergen peptides and activate allergen-specific T cells to proliferate and produce TH2-like cytokines. J. Allergy Clin. Immunol. 120, 1418–1424 (2007).

  29. 29.

    Skokos, D. et al. Mast cell-dependent B and T lymphocyte activation is mediated by the secretion of immunologically active exosomes. J. Immunol. 166, 868–876 (2001).

  30. 30.

    Karlsson, M. R., Kahu, H., Hanson, L. A., Telemo, E. & Dahlgren, U. I. An established immune response against ovalbumin is suppressed by a transferable serum factor produced after ovalbumin feeding: a role of CD25+ regulatory cells. Scand. J. Immunol. 55, 470–477 (2002).

  31. 31.

    Deng, Z. et al. Enterobacteria-secreted particles induce production of exosome-like S1P-containing particles by intestinal epithelium to drive Th17-mediated tumorigenesis. Nat. Commun. 6, 6956 (2015).

  32. 32.

    Kovacikova, Z., Neumannova, K., Rydlova, J., Bizovská, L. & Janura, M. The effect of balance training intervention on postural stability in children with asthma. J. Asthma 55, 502–510 (2017). 0.

  33. 33.

    Lowe, A. P. P. et al. Route of administration affects corticosteroid sensitivity of a combined ovalbumin and lipopolysaccharide model of asthma exacerbation in guinea pigs. J. Pharmacol. Exp. Ther. 362, 327–337 (2017).

  34. 34.

    Prado, N. et al. Exosomes from bronchoalveolar fluid of tolerized mice prevent allergic reaction. J. Immunol. 181, 1519–1525 (2008).

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Acknowledgements

This work was supported by the Program for Innovative Research Team at Chongqing University, 2013.

Author information

Affiliations

  1. Department of Pediatric Respiratory Medicine, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, China

    • Feng-Xia Ding
    • , Wen-Jing Zou
    • , Qu-bei Li
    • , Dai-yin Tian
    •  & Zhou Fu
  2. Ministry of Education Key Laboratory of Child Development and Disorder, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Child Infection and Immunity, Chongqing, 400014, China

    • Feng-Xia Ding
    • , Bo Liu
    • , Wen-Jing Zou
    • , Qu-bei Li
    • , Dai-yin Tian
    •  & Zhou Fu
  3. Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, China

    • Bo Liu

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The authors declare no competing interests.

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Correspondence to Zhou Fu.

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DOI

https://doi.org/10.1038/s41390-018-0020-1