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Infection and Immunity, July 2007, p. 3506-3515, Vol. 75, No. 7
0019-9567/07/$08.00+0     doi:10.1128/IAI.00277-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Leishmania major Abrogates Gamma Interferon-Induced Gene Expression in Human Macrophages from a Global Perspective{triangledown} ,{dagger}

Nisha Dogra, Corinna Warburton, and W. Robert McMaster*

Immunity and Infection Research Centre, Vancouver Coastal Health Research Institute, and the Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada

Received 20 February 2007/ Returned for modification 15 March 2007/ Accepted 20 April 2007

Infection with Leishmania major triggers several pathways in the host cell that are crucial to initial infection as well as those that are used by Leishmania to enhance its replication and virulence. To identify the molecular events of the host cell in response to Leishmania, the global gene expression of the human monocytic cell line THP-1 either infected with Leishmania major in the presence and absence of gamma interferon (IFN-{gamma}) or in the presence of IFN-{gamma} alone was analyzed using high-density human oligonucleotide microarrays, followed by statistical analysis. The persistence of the parasite despite an extensive response to IFN-{gamma}, added 24 h after infection with L. major, suggests that L. major can survive in an IFN-{gamma}-enriched environment in vitro. Results demonstrate that L. major counteracts the IFN-{gamma} response in macrophages on a large scale. Expression of genes involved in the innate immune response, cell adhesion, proteasomal degradation, Toll-like receptor expression, a variety of signaling molecules, and matrix metalloproteinases was significantly modulated.


* Corresponding author. Mailing Address: Jack Bell Research Centre, 451-2660 Oak Street, Vancouver, BC, Canada V6H 3Z6. Phone: (604) 875-4134. Fax: (604) 875-5606. E-mail: robm{at}interchange.ubc.ca

{triangledown} Published ahead of print on 30 April 2007.

{dagger} Supplemental material for this article is available at http://iai.asm.org/.

Editor: W. A. Petri, Jr.


Infection and Immunity, July 2007, p. 3506-3515, Vol. 75, No. 7
0019-9567/07/$08.00+0     doi:10.1128/IAI.00277-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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