Skip Navigation



JAC Advance Access published online on January 13, 2005
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh542
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
55/2/214    most recent
dkh542v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Bellocchio, S.
Right arrow Articles by Romani, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bellocchio, S.
Right arrow Articles by Romani, L.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

JAC © The British Society for Antimicrobial Chemotherapy 2005; all rights reserved
Received September 17, 2004
Revised November 18, 2004
Accepted November 19, 2004

Original article

Liposomal amphotericin B activates antifungal resistance with reduced toxicity by diverting Toll-like receptor signalling from TLR-2 to TLR-4

Silvia Bellocchio 1, Roberta Gaziano 1, Silvia Bozza 1, Giordano Rossi 1, Claudia Montagnoli 1, Katia Perruccio 2, Mario Calvitti 3, Lucia Pitzurra 1, and Luigina Romani 1*

1 Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
2 Division of Hematology, Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
3 Histology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy

* To whom correspondence should be addressed.
Luigina Romani, E-mail: lromani{at}unipg.it


  Abstract

Objectives: Neutrophils play a crucial role in the control of the Aspergillus fumigatus infection and act in concert with antifungal drugs. This study was undertaken to obtain insights into the possible involvement of Toll-like receptors (TLRs) in the interaction of liposomal amphotericin B (L-AmB; AmBisome) with neutrophils in response to A. fumigatus.

Methods: For generation of bone marrow-transplanted mice, irradiated C57BL6 mice were infused with T cell-depleted allogeneic donor cells. For infection, mice were injected intranasally with Aspergillus fumigatus conidia and treated with L-Amb and deoxycholate amphotericin B prophylactically or therapeutically. For TLR-dependent antifungal functions, murine neutrophils were preincubated with antifungals or TLR ligands before the addition of Aspergillus conidia.

Results: The results show that: (a) neutrophil activation by Aspergillus occurs through TLR signalling pathways differently affecting the oxidative and non-oxidative mechanisms of the killing machinery; (b) by diverting signalling from TLR-2 to TLR-4, liposomes of AmBisome activate neutrophils to an antifungal state while attenuating the pro-inflammatory effects of deoxycholate amphotericin B; (c) this translates in vivo to the optimization of the AmBisome therapeutic efficacy in mice with aspergillosis.

Conclusions: These results provide a putative molecular basis for the reduced infusion-related toxicity of AmBisome and suggest that TLR manipulation in vivo is amenable to the induction of optimal microbicidal activity in the absence of inflammatory cytotoxicity to host cells.

Keywords: AmBisome; Aspergillus fumigatus; neutrophils.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 NEJMHome page
S. M. Levitz, S. Shoham, J. D. Cleary, C. Cervera, A. Moreno, F. Lozano, Y. Asakura, T. Komatsu, P.-Y. Bochud, K. A. Marr, et al.
Toll-like Receptor 4 Polymorphisms and Aspergillosis
N. Engl. J. Med., February 5, 2009; 360(6): 634 - 636.
[Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
M. Simitsopoulou, E. Roilides, F. Paliogianni, C. Likartsis, J. Ioannidis, K. Kanellou, and T. J. Walsh
Immunomodulatory Effects of Voriconazole on Monocytes Challenged with Aspergillus fumigatus: Differential Role of Toll-Like Receptors
Antimicrob. Agents Chemother., September 1, 2008; 52(9): 3301 - 3306.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. Banerjee, M. De, and N. Ali
Complete Cure of Experimental Visceral Leishmaniasis with Amphotericin B in Stearylamine-Bearing Cationic Liposomes Involves Down-Regulation of IL-10 and Favorable T Cell Responses
J. Immunol., July 15, 2008; 181(2): 1386 - 1398.
[Abstract] [Full Text] [PDF]

Home page
 J Antimicrob ChemotherHome page
J. Dotis, M. Simitsopoulou, M. Dalakiouridou, T. Konstantinou, C. Panteliadis, T. J. Walsh, and E. Roilides
Amphotericin B formulations variably enhance antifungal activity of human neutrophils and monocytes against Fusarium solani: comparison with Aspergillus fumigatus
J. Antimicrob. Chemother., April 1, 2008; 61(4): 810 - 817.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
E. Orciuolo, M. Stanzani, M. Canestraro, S. Galimberti, G. Carulli, R. Lewis, M. Petrini, and K. V. Komanduri
Effects of Aspergillus fumigatus gliotoxin and methylprednisolone on human neutrophils: implications for the pathogenesis of invasive aspergillosis
J. Leukoc. Biol., October 1, 2007; 82(4): 839 - 848.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
R. E. Lewis, G. Chamilos, R. A. Prince, and D. P. Kontoyiannis
Pretreatment with Empty Liposomes Attenuates the Immunopathology of Invasive Pulmonary Aspergillosis in Corticosteroid-Immunosuppressed Mice
Antimicrob. Agents Chemother., March 1, 2007; 51(3): 1078 - 1081.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
D. C. Sheppard, J. R. Graybill, L. K. Najvar, L. Y. Chiang, T. Doedt, W. R. Kirkpatrick, R. Bocanegra, A. C. Vallor, T. F. Patterson, and S. G. Filler
Standardization of an experimental murine model of invasive pulmonary aspergillosis.
Antimicrob. Agents Chemother., October 1, 2006; 50(10): 3501 - 3503.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
B. H. Segal and T. J. Walsh
Current Approaches to Diagnosis and Treatment of Invasive Aspergillosis
Am. J. Respir. Crit. Care Med., April 1, 2006; 173(7): 707 - 717.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.