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Infection and Immunity, May 2009, p. 2184-2192, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01455-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Modulation of Toll-Like Receptor 2 (TLR2) and TLR4 Responses by Aspergillus fumigatus{triangledown}

Louis Y. A. Chai,1,2,3 Bart Jan Kullberg,1,2 Alieke G. Vonk,4 Adilia Warris,2,5 Alessandra Cambi,6 Jean-Paul Latgé,7 Leo A. B. Joosten,1,2 Jos W. M. van der Meer,1,2 and Mihai G. Netea1,2*

Departments of Medicine,1 Pediatrics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands,5 Nijmegen Institute for Infection, Inflammation and Immunity (N4i), P.O. Box 9101, Geert Grootplein, 6525 GA, Nijmegen, The Netherlands,2 Department of Medicine, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074,3 Erasmus MC, University Medical Center Rotterdam, Department of Medical Microbiology and Infectious Diseases, s-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands,4 Department of Tumour Immunology, Nijmegen Center for Molecular Life Sciences, Radboud University, Nijmegen, The Netherlands,6 Unite des Aspergillus, Institut Pasteur, 25, rue du Dr Roux, 75015 Paris, France7

Received 28 November 2008/ Returned for modification 13 December 2008/ Accepted 31 January 2009

Toll-like receptor (TLR)-based signaling pathways in the host may be modulated by pathogens during the course of infection. We describe a novel immunomodulatory mechanism in which Aspergillus fumigatus conidia induce attenuation of TLR2- and TLR4-mediated interleukin (IL)-6 and IL-1β proinflammatory responses in human mononuclear cells with suppression of IL-1β mRNA transcription. Background TLR2 and TLR4 mRNA transcription was not influenced. A. fumigatus conidia induced TLR2 internalization and uptake into the phagosome with a resultant decrease in surface receptor expression. A. fumigatus hyphae, on the other hand, selectively downregulated the TLR4-mediated response. These novel immunosuppressive effects may facilitate the invasiveness of A. fumigatus.

* Corresponding author. Mailing address: Department of Medicine (463), Radboud University Nijmegen Medical Center, P.O. Box 9101, Geert Grootplein 8, 6525 GA Nijmegen, The Netherlands. Phone: 31-24-3618819. Fax: 31-24-3541734. E-mail: M.Netea{at}aig.umcn.nl

{triangledown} Published ahead of print on 9 February 2009.

Editor: A. Casadevall

Infection and Immunity, May 2009, p. 2184-2192, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01455-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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