Interactions of human immature dendritic cells with de64257; ned recombinant Aspergillus fumigatus antigens

Ref ID: 18578

Author:

M. Ok (1), O. Kurzai (2), F. Ebel (3), C. Baeuerlein (1),
M. Mezger (1), M. Topp (1), H. Einsele (1), J. Loef64258; er (1)

Author address:

(1)Medcal Hospital (Wurzburg, DE); (2)Institut für Hygiene und
Mikrobiologie (Wurzburg, DE); (3)Max von Pettenkofer Institut
(Munich, DE)

Full conference title:

Annual Meeting of the EBMT, 36th

Abstract:

Objectives: One of the major life threatening fungal infections
associated with allogeneic stem cell or bone marrow transplantation is invasive aspergillosis (IA). Dendritic cells represent an
important element of the innate immune system in the defence
against Aspergilli; they acquire antigens in the periphery,
migrate into secondary lymphoid tissues, activate T-cells and
maturate and secrete cytokines and chemokines. Up until now,
the infl uence of distinct Aspergillus fumigatus molecules on the
human innate immune system is largely unexplored.
Methods: We have characterized the interaction between the
A. fumigatus antigens Aspf1 and Crf1 and human monocytederived immature dendritic cells (iDC), respectively. Antigens
were recombinantly expressed in the Pichia pastoris system
and subsequently used for stimulation experiments, which
allowed quantifying gene expression (by qRT-PCR) and secretion of cytokines and chemokines (by ELISA assays) in iDC, to
localize microscopically Aspf1 and to determine its capacity to
induce apoptosis in iDCs. Furthermore, by mixed lymphocyte
reactions (MLR), we have analyzed whether iDCs loaded with
Aspf1 are able to induce T-cell proliferation.
Results: Compared to Crf1, Aspf1 showed a high ability to
specifi cally stimulate iDCs as demonstrated by an increased
expression of genes encoding for pro-infl ammatory cytokines
(e.g. IL-12p35, TNFa) and chemokines (CXCL10, CCL20, IL-
8). By using germlings of a deletion mutant for Aspf1 (dAspf1)
in confrontation assays with iDCs, increased protein secretion compared to stimulation with wild type morphologies was
detectable. Apoptosis of iDCs was markedly induced after cocultivation with Aspf1. MLR revealed that iDCs were not able to
present Aspf1 to autologous T-cells.
Conclusion: This study demonstrates that recombinant A. fumigatus antigens are able to effi ciently stimulate iDCs in vitro;
these observations might potentially lead to the development
of a new therapeutic and/or prophylactic option to prevent and
treat this devastating infection in high risk patients after allogeneic stem cell transplantation.

Abstract Number: P732

Conference Year: 2010

Link to conference website: NULL

New link: NULL

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