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Blood, 15 March 2005, Vol. 105, No. 6, pp. 2258-2265. Prepublished online as a Blood First Edition Paper on November 16, 2004; DOI 10.1182/blood-2004-09-3421. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-09-3421v1 105/6/2258    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Stanzani, M. Articles by Komanduri, K. V. Search for Related Content PubMed PubMed Citation Articles by Stanzani, M. Articles by Komanduri, K. V. Related Collections Hemostasis, Thrombosis, and Vascular Biology Phagocytes Apoptosis Plenary Papers Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLENARY PAPERS Aspergillus fumigatus suppresses the human cellular immune response via gliotoxin-mediated apoptosis of monocytes Marta Stanzani, Enrico Orciuolo, Russell Lewis, Dimitrios P. Kontoyiannis, Sergio L. R. Martins, Lisa S. St. John, and Krishna V. Komanduri From the Transplant Immunology Section, Department of Blood and Marrow Transplantation, M.D. Anderson Cancer Center, Houston, TX; Institute of Hematology-Seragnoli, University of Bologna, Italy; the Department of Oncology, Transplant and Advances in Medicine, University of Pisa, Italy; the Department of Infectious Diseases Infection Control and Employee Health, M.D. Anderson Cancer Center, Houston, TX; Department of Hematology, Fleury-Diagnostic Medical Center, Sao Paulo, Brazil. Aspergillus fumigatus (AF) is a ubiquitous mold and is the most common cause of invasive aspergillosis, an important source of morbidity and mortality in immunocompromised hosts. Using cytokine flow cytometry, we assessed the magnitude of functional CD4+ and CD8+ T-cell responses following stimulation with Aspergillus antigens. Relative to those seen with cytomegalovirus (CMV) or superantigen stimulation, responses to Aspergillus antigens were near background levels. Subsequently, we confirmed that gliotoxin, the most abundant mycotoxin produced by AF, was able to suppress functional T-cell responses following CMV or staphylococcal enterotoxin B (SEB) stimulation. Additional studies demonstrated that crude AF filtrates and purified gliotoxin inhibited antigen-presenting cell function and induced the preferential death of monocytes, leading to a marked decrease in the monocyte-lymphocyte ratio. Analysis of caspase-3 activation confirmed that gliotoxin preferentially induced apoptosis of monocytes; similar effects were observed in CD83+ monocyte-derived dendritic cells. Importantly, the physiologic effects of gliotoxin in vitro were observed below concentrations recently observed in the serum of patients with invasive aspergillosis. These studies suggest that the production of gliotoxin by AF may constitute an important immunoevasive mechanism that is mediated by direct effects on antigen-presenting cells and both direct and indirect effects on T cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Mouldy oldy: how fungus lives among us Brahm H. Segal Blood 2005 105: 2239-2240. [Full Text] [PDF] This article has been cited by other articles: G. Chamilos, R. E. Lewis, G. A. Lamaris, N. D. Albert, and D. P. Kontoyiannis Genomewide Screening for Genes Associated with Gliotoxin Resistance and Sensitivity in Saccharomyces cerevisiae Antimicrob. Agents Chemother., April 1, 2008; 52(4): 1325 - 1329. [Abstract] [Full Text] [PDF] J. Tao, B. H. Segal, C. Eppolito, Q. Li, C. G. Dennis, R. Youn, and P. A. Shrikant Aspergillus fumigatus extract differentially regulates antigen-specific CD4+ and CD8+ T cell responses to promote host immunity J. Leukoc. Biol., September 1, 2006; 80(3): 529 - 537. [Abstract] [Full Text] [PDF] R. A. Cramer Jr., M. P. Gamcsik, R. M. Brooking, L. K. Najvar, W. R. Kirkpatrick, T. F. Patterson, C. J. Balibar, J. R. Graybill, J. R. Perfect, S. N. Abraham, et al. Disruption of a Nonribosomal Peptide Synthetase in Aspergillus fumigatus Eliminates Gliotoxin Production Eukaryot. Cell, June 1, 2006; 5(6): 972 - 980. [Abstract] [Full Text] [PDF] O. Beck, M. S. Topp, U. Koehl, E. Roilides, M. Simitsopoulou, M. Hanisch, J. Sarfati, J. P. Latge, T. Klingebiel, H. Einsele, et al. Generation of highly purified and functionally active human TH1 cells against Aspergillus fumigatus Blood, March 15, 2006; 107(6): 2562 - 2569. [Abstract] [Full Text] [PDF] V. Gafa, R. Lande, M. C. Gagliardi, M. Severa, E. Giacomini, M. E. Remoli, R. Nisini, C. Ramoni, P. Di Francesco, D. Aldebert, 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., March 1, 2006; 74(3): 1480 - 1489. [Abstract] [Full Text] [PDF] R. E. Lewis, N. P. Wiederhold, M. S. Lionakis, R. A. Prince, and D. P. Kontoyiannis Frequency and Species Distribution of Gliotoxin-Producing Aspergillus Isolates Recovered from Patients at a Tertiary-Care Cancer Center J. Clin. Microbiol., December 1, 2005; 43(12): 6120 - 6122. [Abstract] [Full Text] [PDF]

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