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Blood, 1 June 2004, Vol. 103, No. 11, pp. 4232-4239. Prepublished online as a Blood First Edition Paper on February 24, 2004; DOI 10.1182/blood-2003-11-4036. This Article Full Text (PDF) All Versions of this Article: 2003-11-4036v1 103/11/4232    most recent Alert me when this article is cited Alert me if a correction is posted 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 Romani, L. Articles by Garaci, E. Search for Related Content PubMed PubMed Citation Articles by Romani, L. Articles by Garaci, E. Social Bookmarking                   What's this? Submitted November 25, 2003 Accepted February 6, 2004 Thymosin 1 activates dendritic cells for antifungal Th1 resistance through toll-like receptor signaling Luigina Romani*, Francesco Bistoni, Roberta Gaziano, Silvia Bozza, Claudia Montagnoli, Katia Perruccio, Lucia Pitzurra, Silvia Bellocchio, Andrea Velardi, Guido Rasi, Paolo di Franceso, and Enrico Garaci Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy Division of Hematology, Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy Institute of Neurobiology and Molecular Medicine, CNR, Roma, Italy Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Tor Vergata, Roma, Italy * Corresponding author; email: lromani{at}unipg.it. Dendritic cells (DCs) show a remarkable functional plasticity in the recognition of Aspergillus fumigatus and orchestrate the antifungal immune resistance in the lungs. Here we show that thymosin 1, a naturally occurring thymic peptide, induces functional maturation and interleukin-12 production by fungus-pulsed DCs through the p38 mitogen-activated protein kinase/NF-B-dependent pathway. This occurs by signaling through the myeloid differentiation factor 88-dependent pathway involving distinct Toll-like receptors. In vivo, the synthetic peptide activates T-helper (Th) cell 1-dependent antifungal immunity, accelerates myeloid cell recovery and protects highly susceptible hematopoietic transplanted mice from aspergillosis. By revealing the unexpected activity of an old molecule, our finding provide the rationale for its therapeutic prescriptions and qualify the synthetic peptide as a candidate adjuvant promoting the coordinated activation of the innate and adaptive Th immunity to the fungus. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. J. Park and B. Mehrad Innate Immunity to Aspergillus Species Clin. Microbiol. Rev., October 1, 2009; 22(4): 535 - 551. [Abstract] [Full Text] [PDF] E. J. Cornish, B. J. Hurtgen, K. McInnerney, N. L. Burritt, R. M. Taylor, J. N. Jarvis, S. Y. Wang, and J. B. Burritt Reduced Nicotinamide Adenine Dinucleotide Phosphate Oxidase-Independent Resistance to Aspergillus fumigatus in Alveolar Macrophages J. Immunol., May 15, 2008; 180(10): 6854 - 6867. [Abstract] [Full Text] [PDF] S. Bozza, R. Gaziano, P. Bonifazi, T. Zelante, L. Pitzurra, C. Montagnoli, S. Moretti, R. Castronari, P. Sinibaldi, G. Rasi, et al. Thymosin {alpha}1 activates the TLR9/MyD88/IRF7-dependent murine cytomegalovirus sensing for induction of anti-viral responses in vivo Int. Immunol., November 1, 2007; 19(11): 1261 - 1270. [Abstract] [Full Text] [PDF] B. H. Segal Role of Macrophages in Host Defense Against Aspergillosis and Strategies for Immune Augmentation Oncologist, October 1, 2007; 12(suppl_2): 7 - 13. [Abstract] [Full Text] [PDF] L. Romani, F. Bistoni, K. Perruccio, C. Montagnoli, R. Gaziano, S. Bozza, P. Bonifazi, G. Bistoni, G. Rasi, A. Velardi, et al. Thymosin {alpha}1 activates dendritic cell tryptophan catabolism and establishes a regulatory environment for balance of inflammation and tolerance Blood, October 1, 2006; 108(7): 2265 - 2274. [Abstract] [Full Text] [PDF] A. Mosoian, A. Teixeira, A. A. High, R. E. Christian, D. F. Hunt, J. Shabanowitz, X. Liu, and M. 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Romani Immunity and Tolerance to Aspergillus Involve Functionally Distinct Regulatory T Cells and Tryptophan Catabolism J. Immunol., February 1, 2006; 176(3): 1712 - 1723. [Abstract] [Full Text] [PDF] S. Bellocchio, S. Moretti, K. Perruccio, F. Fallarino, S. Bozza, C. Montagnoli, P. Mosci, G. B. Lipford, L. Pitzurra, and L. Romani TLRs Govern Neutrophil Activity in Aspergillosis J. Immunol., December 15, 2004; 173(12): 7406 - 7415. [Abstract] [Full Text] [PDF] L. Pitzurra, S. Bellocchio, A. Nocentini, P. Bonifazi, R. Scardazza, L. Gallucci, F. Stracci, C. Simoncelli, F. Bistoni, and L. Romani Antifungal Immune Reactivity in Nasal Polyposis Infect. Immun., December 1, 2004; 72(12): 7275 - 7281. [Abstract] [Full Text] [PDF]

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