Intranasally delivered siRNA targeting PI3K/Akt/mTOR inflammatory pathways protects from aspergillosis

Mucosal Immunology

Volumn 3, Issue 2, 2010, Pages 193-205

  Bonifazi, P ^a   D'Angelo, C ^a   Zagarella, S ^a   Zelante, T ^a   Bozza, S ^a   De Luca, A ^a   Giovannini, G ^a   Moretti, S ^a   Iannitti, R G ^a   Fallarino, F ^a   Carvalho, A ^a   Cunha, C ^a   Bistoni, F ^a   Romani, L ^a  

^a UNIVERSITY OF PERUGIA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

INDOLEAMINE 2,3 DIOXYGENASE; MAMMALIAN TARGET OF RAPAMYCIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; SMALL INTERFERING RNA; STAT3 PROTEIN;

ADOPTIVE TRANSFER; ALLERGY; ANIMAL CELL; ANIMAL CELL CULTURE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASPERGILLUS FUMIGATUS; CONIDIUM; CONTROLLED STUDY; DENDRITIC CELL; ENZYME LINKED IMMUNOSORBENT ASSAY; FEMALE; FLOW CYTOMETRY; FUNGAL STRAIN; FUNGUS HYPHAE; HISTOPATHOLOGY; IN VITRO STUDY; IN VIVO STUDY; LUNG ASPERGILLOSIS; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTECTION; REGULATORY T LYMPHOCYTE; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; WESTERN BLOTTING;

EID: 77249102130     PISSN: 19330219     EISSN: None     Source Type: Journal    
DOI: 10.1038/mi.2009.130     Document Type: Article

References (58)

1. Marr, K. A., Patterson, T. & Denning, D. Aspergillosis. Pathogenesis, clinical manifestations, and therapy. Infect. Dis. Clin. North Am. 16, 875-894vi (2002).
2. Denning, D. W., O ' Driscoll, B. R., Hogaboam, C. M., Bowyer, P. & Niven, R. M. The link between fungi and severe asthma: a summary of the evidence. Eur. Respir. J. 27, 615-626 (2006).
3. Romani, L., Zelante, T., De Luca, A., Fallarino, F. & Puccetti, P. IL-17 and therapeutic kynurenines in pathogenic infl ammation to fungi. J. Immunol. 180, 5157-5162 (2008).
4. Romani, L. et al. Defective tryptophan catabolism underlies infl ammation in mouse chronic granulomatous disease. Nature 451, 211-215 (2008).
5. Ortega, M. et al. Prospective evaluation of procalcitonin in adults with nonneutropenic fever after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 37, 499-502 (2006).
6. Schubert, M. S. Allergic fungal sinusitis. Clin. Rev. Allergy Immunol. 30, 205-216 (2006).
7. Romani, L. in Aspergillus and Aspergillosis (eds. Latg è, J. P. & Steinbach, W.J.) 247-261 (ASM Press: Washington D.C., USA, 2008).
8. Bozza, S. et al. Dendritic cells transport conidia and hyphae of Aspergillus fumigatus from the airways to the draining lymph nodes and initiate disparate Th responses to the fungus. J. Immunol. 168, 1362-1371 (2002).
9. Bozza, S. et al. A dendritic cell vaccine against invasive aspergillosis in allogeneic hematopoietic transplantation. Blood 102, 3807-3814 (2003).
10. Romani, L. et al. Thymosin alpha1 activates dendritic cell tryptophan catabolism and establishes a regulatory environment for balance of infl ammation and tolerance. Blood 108, 2265-2274 (2006).
11. Montagnoli, C. et al. Immunity and tolerance to Aspergillus involve functionally distinct regulatory T cells and tryptophan catabolism. J. Immunol. 176, 1712-1723 (2006).
12. Mezger, M. et al. Proinfl ammatory response of immature human dendritic cells is mediated by dectin-1 after exposure to Aspergillus fumigatus germ tubes. J. Infect. Dis. 197, 924-931 (2008).
13. Serrano-Gomez, D. et al. Dendritic cell-specifi c intercellular adhesion molecule 3-grabbing nonintegrin mediates binding and internalization of Aspergillus fumigatus conidia by dendritic cells and macrophages. J Immunol 173, 5635-5643 (2004).
14. Bellocchio, S. et al. The contribution of the Toll-like/IL-1 receptor superfamily to innate and adaptive immunity to fungal pathogens in vivo. J. Immunol. 172, 3059-3069 (2004).
15. GeurtsvanKessel, C. H. & Lambrecht, B. N. Division of labor between dendritic cell subsets of the lung. Mucosal. Immunol. 1, 442-450 (2008).
16. Grohmann, U. et al. Reverse signaling through GITR ligand enables dexamethasone to activate IDO in allergy. Nat. Med. 13, 579-586 (2007).
17. Zelante, T. et al. IL-23 and the Th17 pathway promote infl ammation and impair antifungal immune resistance. Eur. J. Immunol. 37, 2695-2706 (2007).
18. van Rijt, L. S. et al. In vivo depletion of lung CD11c+ dendritic cells during allergen challenge abrogates the characteristic features of asthma. J. Exp. Med. 201, 981-991 (2005).
19. Bonifazi, P. et al. Balancing infl ammation and tolerance in vivo through dendritic cells by the commensal Candida albicans. Mucosal. Immunol. 2, 362-374 (2009).
20. Weichhart, T. et al. The TSC-mTOR signaling pathway regulates the innate infl ammatory response. Immunity 29, 565-577 (2008).
21. Weichhart, T. & Saemann, M. D. The multiple facets of mTOR in immunity. Trends Immunol. 30, 218-226 (2009).
22. Fukao, T. et al. PI3K-mediated negative feedback regulation of IL-12 production in DCs. Nat. Immunol. 3, 875-881 (2002).
23. Martin, M., Rehani, K., Jope, R. S. & Michalek, S. M. Toll-like receptormediated cytokine production is differentially regulated by glycogen synthase kinase 3. Nat. Immunol. 6, 777-784 (2005).
24. Cao, W. et al. Toll-like receptor-mediated induction of type I interferon in plasmacytoid dendritic cells requires the rapamycin-sensitive PI(3)KmTOR- p70S6K pathway. Nat. Immunol. 9, 1157-1164 (2008).
25. Bonizzi, G. & Karin, M. The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends Immunol. 25, 280-288 (2004).
26. Barton, B. E. STAT3: a potential therapeutic target in dendritic cells for the induction of transplant tolerance. Expert Opin. Ther Targets 10, 459-470 (2006).
27. Nadiminty, N. et al. Stat3 activation of NF-{kappa}B p100 processing involves CBP/p300-mediated acetylation. Proc. Natl. Acad. Sci. USA 103, 7264-7269 (2006).
28. Tas, S. W. et al. Noncanonical NF-kappaB signaling in dendritic cells is required for indoleamine 2,3-dioxygenase (IDO) induction and immune regulation. Blood 110, 1540-1549 (2007).
29. Mellor, A. L. & Munn, D. H. IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat. Rev. Immunol. 4, 762-774 (2004).
30. Puccetti, P. & Grohmann, U. IDO and regulatory T cells: a role for reverse signalling and non-canonical NF-kappaB activation. Nat. Rev. Immunol. 7, 817-823 (2007).
31. Gafa, V. et al. Human dendritic cells following Aspergillus fumigatus infection express the CCR7 receptor and a differential pattern of interleukin-12 (IL-12), IL-23, and IL-27 cytokines, which lead to a Th1 response. Infect. Immun. 74, 1480-1489 (2006).
32. Amsen, D. et al. Instruction of distinct CD4T helper cell fates by different notch ligands on antigen-presenting cells. Cell 117, 515-526 (2004).
33. Smit, J. J., Rudd, B. D. & Lukacs, N. W. Plasmacytoid dendritic cells inhibit pulmonary immunopathology and promote clearance of respiratory syncytial virus. J. Exp. Med. 203, 1153-1159 (2006).
34. Blasius, A. L., Cella, M., Maldonado, J., Takai, T. & Colonna, M. Siglec-H is an IPC-specifi c receptor that modulates type I IFN secretion through DAP12. Blood 107, 2474-2476 (2006).
35. Laouar, Y., Welte, T., Fu, X. Y. & Flavell, R. A. STAT3 is required for Flt3L-dependent dendritic cell differentiation. Immunity 19, 903-912 (2003).
36. McGee, H. S., Edwan, J. H. & Agrawal, D. K. Flt3-L Increases CD4+CD25+Foxp3+ICOS+ cells in the lung of cockroach-sensitized and challenged mice. Am J Respir Cell Mol Biol (2009); (e-pub ahead of print).
37. LoPiccolo, J., Blumenthal, G. M., Bernstein, W. B. & Dennis, P. A. Targeting the PI3K/Akt/mTOR pathway: effective combinations and clinical considerations. Drug Resist Updat 11, 32-50 (2008).
38. Ruiter, G. A., Zerp, S. F., Bartelink, H., van Blitterswijk, W. J. & Verheij, M. Alkyl-lysophospholipids activate the SAPK/JNK pathway and enhance radiation-induced apoptosis. Cancer Res 59, 2457-2463 (1999).
39. Behlke, M. A. Progress towards in vivo use of siRNAs. Mol. Ther. 13, 644-670 (2006).
40. Brazil, D. P., Yang, Z. Z. & Hemmings, B. A. Advances in protein kinase B signalling: AKTion on multiple fronts. Trends Biochem. Sci. 29, 233-242 (2004).
41. Moretti, S. et al. The contribution of PARs to infl ammation and immunity to fungi. Mucosal. Immunol. 1, 156-168 (2008).
42. Bozza, S. et al. Lack of Toll IL-1R8 exacerbates Th17 cell responses in fungal infection. J. Immunol. 180, 4022-4031 (2008).
43. Delgoffe, G. M. et al. The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment. Immunity 30, 832-844 (2009).
44. Haxhinasto, S., Mathis, D. & Benoist, C. The AKT-mTOR axis regulates de novo differentiation of CD4+Foxp3+ cells. J. Exp. Med. 205, 565-574 (2008).
45. Sauer, S. et al. T cell receptor signaling controls Foxp3 expression via PI3K, Akt, and mTOR. Proc. Natl. Acad. Sci. USA 105, 7797-7802 (2008).
46. Rivera, A. et al. Innate immune activation and CD4+ T cell priming during respiratory fungal infection. Immunity 25, 665-675 (2006).
47. Ramaprakash, H., Ito, T., Standiford, T. J., Kunkel, S. L. & Hogaboam, C. M. Toll-like receptor 9 modulates immune responses to Aspergillus fumigatus conidia in immunodefi cient and allergic mice. Infect. Immun. 77, 108-119 (2009).
48. Hohl, T. M. et al. Aspergillus fumigatus triggers infl ammatory responses by stage-specifi c beta-glucan display. PLoS Pathog 1, e30 (2005).
49. Gringhuis, S. I. et al. Dectin-1 directs T helper cell differentiation by controlling noncanonical NF-kappaB activation through Raf-1 and Syk. Nat. Immunol. 10, 203-213 (2009).
50. Beurel, E. & Jope, R. S. Differential regulation of STAT family members by glycogen synthase kinase-3. J. Biol. Chem. 283, 21934-21944 (2008).
51. Bitko, V. & Barik, S. Nasal delivery of siRNA. Methods Mol. Biol. 442, 75-82 (2008).
52. Zhang, W. et al. Inhibition of respiratory syncytial virus infection with intranasal siRNA nanoparticles targeting the viral NS1 gene. Nat. Med. 11, 56-62 (2005).
53. Gardy, J. L., Lynn, D. J., Brinkman, F. S. & Hancock, R. E. Enabling a systems biology approach to immunology: focus on innate immunity. Trends Immunol. 30, 249-262 (2009).
54. Lebeis, S. L. & Kalman, D. Aligning antimicrobial drug discovery with complex and redundant host-pathogen interactions. Cell Host Microbe 5, 114-122 (2009).
55. Aimanianda, V. et al. Surface hydrophobin prevents immune recognition of airborne fungal spores. Nature 460, 1117-1121 (2009).
56. Asselin-Paturel, C., Brizard, G., Pin, J. J., Briere, F. & Trinchieri, G. Mouse strain differences in plasmacytoid dendritic cell frequency and function revealed by a novel monoclonal antibody. J. Immunol. 171, 6466-6477 (2003).
57. Stephens-Romero, S. D., Mednick, A. J. & Feldmesser, M. The pathogenesis of fatal outcome in murine pulmonary aspergillosis depends on the neutrophil depletion strategy. Infect. Immun. 73, 114-125 (2005).
58. Zhang, X. et al. Small interfering RNA targeting heme oxygenase-1 enhances ischemia-reperfusion-induced lung apoptosis. J. Biol. Chem. 279, 10677-10684 (2004).