Abstract
Lymphocytes play a major role in host defense against Aspergillus, but little is known about the contribution of dendritic cells (DC) to antifungal immunity in humans. We have observed that DC derived from normal volunteers phagocytose heat-killed A. fumigatusconidia. Following 24 h of exposure to the fungus, DC displayed an increase in the mean fluorescence intensity of HLA-DR, CD80, and CD86, and an increase in the percentage of CD54+ cells. These DC also displayed increased production of IL-12. DC derived from CD34+ progenitors or monocytes stimulated autologous lymphocytes to proliferate and produce high levels of interferon-γ, but not interleukin-10, in response to fungal antigen. DC generated from CD34+ progenitors collected prior to autologous or allogeneic stem cell transplantation also partially restored the in vitro antifungal proliferative response of lymphocytes obtained from patients 1 month after transplantation. These results suggest that DC are important to host–response to A. fumigatus, and that ex vivo-generated DC might be useful in restoring or enhancing the antifungal immunity after hematopoietic stem cell transplantation. Bone Marrow Transplantation (2001) 27, 647–652.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Morrison VA, Haake RJ, Weisdorf DJ . Non-Candida fungal infections after bone marrow transplantation: risk factors and outcome Am J Med 1994 96: 497–503
Wald A, Leisenring W, van Burik JA, Bowden RA . Epidemiology of Aspergillus infections in a large cohort of patients undergoing bone marrow transplantation J Infect Dis 1997 175: 1459–1466
Ho PL, Yuen KY . Aspergillosis in bone marrow transplant recipients Crit Rev Oncol Hematol 2000 34: 55–69
Cenci E, Mencacci A, Fe d'Ostiani C et al. Cytokine- and T-helper dependent lung mucosa immunity in mice with invasive pulmonary aspergillosis J Infect Dis 1998 178: 1750–1760
Cenci E, Mencacci A, Bacci A et al. T cell vaccination in mice with invasive pulmonary aspergillosis J Immunol 2000 165: 381–388
Savary CA, Grazziutti ML, Melichar B et al. Multidimensional flow-cytometric analysis of dendritic cells in peripheral blood of normal donors and cancer patients Cancer Immunol Immunother 1998 45: 234–240
Fearnley DB, Whyte LF, Carnoutsos SA et al. Monitoring human blood dendritic cell numbers in normal individuals and in stem cell transplantation Blood 1999 93: 728–736
Reichert VL, Okada CY, Liso A et al. Idiotype vaccination using dendritic cells after autologous peripheral blood stem cell transplantation for multiple myeloma – a feasibility study Blood 1999 93: 2411–2419
Przepiorka D, van Vlasselaer P, Huynh L et al. Rapid debulking and CD34 enrichment of filgrastim-mobilized peripheral blood stem cells by semiautomated density gradient centrifugation in a closed system J Hematother 1996 5: 497–502
Romani N, Gruner S, Brang D et al. Proliferating dendritic cell progenitors in human blood J Exp Med 1994 180: 83–93
Sallusto F, Lanzavecchia A . Efficient presentation of soluble antigen by cultured human dendritic cells is mantained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor α J Exp Med 1994 179: 1109–1118
Grazziutti ML, Rex JH, Cowart RE et al. Aspergillus fumigatus conidia induce a Th1-type cytokine response J Infect Dis 1997 176: 1579–1583
Martins MD, Rodriguez LJ, Savary CA et al. Activated lymphocytes reduce adherence of Aspergillus fumigatus Med Mycol 1998 36: 281–289
Savary CA, Grazziutti ML, Melichar B et al. Multidimensional flow-cytometric analysis of dendritic cells in peripheral blood of normal donors and cancer patients Cancer Immunol Immunother 1998 45: 234–240
Tollemar J, Ringden O . Early recovery of lymphocyte response to Candida after bone marrow transplantation in colonized patients Bone Marrow Transplant 1991 7: 285–291.
Cenci E, Perito S, Enssle KH et al. Th1 and Th2 cytokines in mice with invasive aspergillosis Infect Immunity 1997 65: 564–570
Cenci E, Mencacci A, Del Sero G et al. Interleukin-4 causes susceptibility to invasive pulmonary aspergillosis through suppression of protective type I responses J Infect Dis 1999 180: 1957–1968
Sallusto F, Cella M, Danieli C, Lanzavecchia A . Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecule in the major histocompatibility complex II compartment: downregulation by cytokines and bacterial products J Exp Med 1995 182: 389–400
Inaba K, Inaba M, Naito M, Steinman RM . Dendritic cell progenitors phagocytose particulates, including Bacillus Calmette–Guerin organisms, and sensitize mice to mycobacterial antigens in vivo J Exp Med 1993 178: 479–488
Mullbacher A, Eichner RD . Immunosuppression in vitro by a metabolite of a human pathogenic fungus Proc Natl Acad Sci USA 1984 81: 3835–3837
Turley SJ, Steinman RM, Mellman I, Inaba K . Propogation and culture of dendritic cells. In: Lotze MT, Thomson AW (eds) Dendritic Cells Academic Press: New York 1999 535–553.
Cella M, Scheidegger D, Palmer-Lehmann K et al. Ligation of CD40 on dendritic cells triggers production of high levels of Interleukin-12 and enhances T cell stimulatory capacity: T–T help via APC activation J Exp Med 1996 184: 747–752
Reis e Sousa C, Hieny S, Scharton-Kersten T et al. In vivo microbial stimulation induces rapid CD40 ligand-independent production of interleukin-12 by dendritic cells and their redistribution to T cell areas J Exp Med 1997 186: 1819–1829
Rooney CM, Smith CA, Ng CY et al. Infusion of cytotoxic T cells for the prevention and treatment of Epstein–Barr virus-induced lymphoma in allogeneic transplant recipients Blood 1998 92: 1549–1555
Acknowledgements
This work was supported in part by grant NAG8–1347 from the National Aeronautics and Space Administration (NASA), subcontract NCC 9–36 under the Texas Medical Center – NASA/Johnson Space Center Cooperative Agreement, grant CA-16672 from the National Cancer Institute, and the Tony Anderson Fund.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Grazziutti, M., Przepiorka, D., Rex, J. et al. Dendritic cell-mediated stimulation of the in vitro lymphocyte response to Aspergillus. Bone Marrow Transplant 27, 647–652 (2001). https://doi.org/10.1038/sj.bmt.1702832
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bmt.1702832
Keywords
This article is cited by
-
Respiratory dendritic cells: mediators of tolerance and immunity
Immunologic Research (2007)
-
Dendritic cells transduced with an adenovirus vector encoding interleukin-12 are a potent vaccine for invasive pulmonary aspergillosis
Genes & Immunity (2005)
-
Immunity to fungal infections
Nature Reviews Immunology (2004)
-
Aspergillus infections in allogeneic stem cell transplant recipients: have we made any progress?
Bone Marrow Transplantation (2002)