Therapeutic modality of plasmacytoid dendritic cells in a murine model of <em>Aspergillus fumigatus</em> sensitized and infected asthma

Hiroto Matsuse; Tohru Yamagishi; Norio Kodaka; Chihiro Nakano; Chizu Fukushima; Yasushi Obase; Hiroshi Mukae

doi:10.3934/Allergy.2017.4.232

AIMS Allergy and Immunology, 2017, 1(4): 232-241. doi: 10.3934/Allergy.2017.4.232. Research article Topical Section

Export file:

Format

RIS(for EndNote,Reference Manager,ProCite)
BibTex
Text

Content

Citation Only
Citation and Abstract

Therapeutic modality of plasmacytoid dendritic cells in a murine model of Aspergillus fumigatus sensitized and infected asthma

Hiroto Matsuse, Tohru Yamagishi, Norio Kodaka, Chihiro Nakano, Chizu Fukushima, Yasushi Obase, Hiroshi Mukae

1 Division of Respiratory Medicine, Department of Internal Medicine, Toho University Ohashi Medical Center, Tokyo, Japan
2 Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan

Received: , Accepted: , Published:

Topical Section: Dendritic Cell Control of Immune Responses

Abstract Full Text(HTML) Figure/Table Related pages

Aspergillus fumigatus (Af) is a representative pathogen for severe asthma with fungal sensitization (SAFS), which has been coined to define a particular phenotype of severe asthma despite the use of high-dose inhaled corticosteroids and long-acting bronchodilators. Since current therapies cannot adequately control SAFS, a new therapeutic modality is required. Focusing on the immunoregulatory profile of plasmacytoid dendritic cells (pDCs), the purpose of the present study was to investigate the effects of intranasal transfer of pDCs to a murine model of Af sensitized and infected asthma mimicking SAFS on airway inflammation and cytokine profiles. Splenic pDCs were obtained from Af sensitized and infected donor mice. Thereafter, these pDCs were intranasally transferred into the airway of Af sensitized and infected recipient mice. pDCs inhibited both eosinophilic and neutrophilic airway inflammation. Analysis of cytokine profiles in lung tissue revealed that pDCs significantly inhibited proinflammatory cytokines, MIP-2, IL-5 and IL-17, and significantly increased an immunoregulatory cytokine, IL-10. In contrast, pDCs did not significantly modulate IFN-γ, a critical cytokine for antifungal immunity, suggesting the absence of immunosuppressive effects. Transfer of pDCs into the airway could be an effective and safe therapeutic modality for SAFS.

Figure/Table

Supplementary

Article Metrics

Keywords: severe asthma with fungal sensitization; Aspergillus fumigates; plasmacytoid dendritic cells; airway inflammation; cytokines

Citation: Hiroto Matsuse, Tohru Yamagishi, Norio Kodaka, Chihiro Nakano, Chizu Fukushima, Yasushi Obase, Hiroshi Mukae. Therapeutic modality of plasmacytoid dendritic cells in a murine model of Aspergillus fumigatus sensitized and infected asthma. AIMS Allergy and Immunology, 2017, 1(4): 232-241. doi: 10.3934/Allergy.2017.4.232

References:

1. Ray A, Oriss TB, Wenzel SE (2015) Emerging molecular phenotypes of asthma. Am J Physiol-Lung C 308: L130–L140.
2. Iii WCA, Apter A, Dutmer CM, et al. (2017) Advances in asthma in 2016: designing individualized approaches to management. J Allergy Clin Immun 140: 671–680.
3. Lemanske RF Jr (2003) Viruses and asthma: inception, exacerbation, and possible prevention. J Pediatr 142: S3–S8.
4. Nicholson KG, Kent J, Ireland DC (1993) Respiratory viruses and exacerbations of asthma in adults. BMJ 307: 982–986.
5. Denning DW, O'Driscoll BR, Hogaboam CM, et al. (2006) The link between fungi and severe asthma: a summary of the evidence. Eur Respir J 27: 615–626.
6. Denning DW, O'Driscoll BR, Powell G, et al. (2009) Randomized controlled trial of oral antifungal treatment for severe asthma with fungal sensitization: the fungal asthma sensitization trial (FAST) study. Am J Resp Crit Care 179: 11–18.
7. Pasqualotto AC, Powell G, Niven R, et al. (2009) The effects of antifungal therapy on severe asthma with fungal sensitization and allergic bronchopulmonary aspergillosis. Respirology 14: 1121–1127.
8. Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392: 245–252.
9. Ghosh S, Hoselton SA, Schuh JM (2015) Allergic inflammation in Aspergillus fumigatus-induced fungal asthma. Curr Allergy Asthm R 15: 59.
10. Loures FV, Röhm M, Lee CK, et al. (2015) Recognition of Aspergillus fumigatus hyphae by human plasmacytoid dendritic cells is mediated by dectin-2 and results in formation of extracellular traps. PLoS Pathog 11: e1004643–e1004665.
11. Vroman H, Hendriks RW, Kool M (2017) Dendritic cell subsets in asthma: impaired tolerance or exaggerated inflammation? Front Immuno 8: 941–951.
12. Steinman RM (2003) Some interfaces of dendritic cell biology. APMIS 111: 675–697.
13. Kondo Y, Matsuse H, Machida I, et al. (2004) Regulation of mite allergen-pulsed murine dendritic cells by respiratory syncytial virus. Am J Resp Crit Care 169: 494–498.
14. Dalod M, Hamilton T, Salomon R, et al. (2003) Dendritic cell responses to early murine cytomegalovirus infection: subset functional specialization and differential regulation by interferon alpha/beta. J Exp Med 197: 885–898.
15. Wang H, Peters N, Schwarze J (2006) Plasmacytoid dendritic cells limit viral replication, pulmonary inflammation, and airway hyperresponsiveness in respiratory syncytial virus infection. J Immunol 177: 6263–6270.
16. Smit JJ, Rudd BD, Lukacs NW (2006) Plasmacytoid dendritic cells inhibit pulmonary immunopathology and promote clearance of respiratory syncytial virus. J Exp Med 203: 1153–1159.
17. Heer HJD, Hammad H, Soullié T, et al. (2004) Essential role of lung plasmacytoid dendritic cells in preventing asthmatic reactions to harmless inhaled antigen. J Exp Med 200: 89–98.
18. Fukushima C, Matsuse H, Fukahori S, et al. (2010) Aspergillus fumigatus synergistically enhances mite-induced allergic airway inflammation. Med Sci Monitor 16: BR197–BR202.
19. Kawano T, Matsuse H, Fukahori S, et al. (2012) Acetaldehyde at a low concentration synergistically exacerbates allergic airway inflammation as an endocrine-disrupting chemical and as a volatile organic compound. Respiration 84: 135–141.
20. Matsuse H, Fukushima C, Fukahori S, et al. (2013) Differential effects of dexamethasone and itraconazole on Aspergillus fumigatus-exacerbated allergic airway inflammation in a murine model of mite-sensitized asthma. Respiration 85: 429–435.
21. O'Driscoll BR, Powell G, Chew F, et al. (2009) Comparison of skin prick tests with specific serum immunoglobulin E in the diagnosis of fungal sensitization in patients with severe asthma. Clin Exp Allergy 39: 1677–1683.
22. Zureik M, Neukirch C, Leynaert B, et al. (2002) Sensitisation to airborne moulds and severity of asthma: cross sectional study from European Community respiratory health survey. BMJ 325: 411–444.
23. Agarwal R (2011) Severe asthma with fungal sensitization. Curr Allergy Asthm R 11: 403–413.
24. Gibson PG, Simpson JL, Saltos N (2001) Heterogeneity of airway inflammation in persistent asthma: evidence of neutrophilic inflammation and increased sputum interleukin-8. Chest 119: 1329–1336.
25. Fairs A, Agbetile J, Hargadon B, et al. (2010) IgE sensitization to Aspergillus fumigatus is associated with reduced lung function in asthma. Am J Resp Crit Care 182: 1362–1368.
26. Hadebe S, Kirstein F, Fierens K, et al. (2015) Microbial ligand costimulation drives neutrophilic steroid-refractory asthma. PLoS One 10: e0134219.
27. Chung KF (2013) New treatments for severe treatment-resistant asthma: targeting the right patient. Lancet Respir Med 1: 639–652.
28. Agbetile J, Bourne M, Fairs A, et al. (2014) Effectiveness of voriconazole in the treatment of Aspergillus fumigatus-associated asthma (EVITA3 study). J Allergy Clin Immun 134: 33–39.
29. Philippe B, Ibrahim-Granet O, Prévost MC, et al. (2003) Killing of Aspergillus fumigatus by alveolar macrophages is mediated by reactive oxidant intermediates. Infect Immun 71: 3034–3042.
30. Machida I, Matsuse H, Kondo Y, et al. (2004) Cysteinyl leukotrienes regulate dendritic cell functions in a murine model of asthma. J Immunol 172: 1833–1838.
31. Kondo Y, Matsuse H, Machida I, et al. (2004) Regulation of mite allergen-pulsed murine dendritic cells by respiratory syncytial virus. Am J Resp Crit Care 169: 494–498.
32. Heer HJD, Hammad H, Soullie T, et al. (2004) Essential role of lung plasmacytoid dendritic cells in preventing asthmatic reactions to harmless inhaled antigen. J Exp Med 200: 89–98.
33. Tsuchida T, Matsuse H, Fukahori S, et al. (2011) Effect of respiratory syncytial virus infection on plasmacytoid dendritic cell-regulation of allergic airway inflammation. Int Arch Allergy Imm 157: 21–30.
34. Duan W, Croft M (2014) Control of regulatory T cells and airway tolerance by lung macrophages and dendritic cells. Ann Am Thorac Soc 11: S306–S313.

show all references

Reader Comments

your name: * your email: *

Copyright Info: 2017, Hiroto Matsuse, et al., licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution Licese (http://creativecommons.org/licenses/by/4.0)

Download full text in PDF

Associated material

Metrics