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Infection and Immunity, March 2008, p. 1186-1192, Vol. 76, No. 3
0019-9567/08/$08.00+0     doi:10.1128/IAI.01320-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Comparison of the Effects of Leishmania major or Leishmania donovani Infection on Macrophage Gene Expression ^,

David J. Gregory,^1, Robert Sladek,² Martin Olivier,¹ and Greg Matlashewski^1*

Department of Microbiology and Immunology, McGill University, 3775 University Sreet, Montreal H3A 2B4, Canada,¹ McGill University and Genome Quebec Innovation Centre, 740 Avenue Dr. Penfield, Montreal H3A 1A4, Canada²

Received 30 September 2007/ Returned for modification 16 November 2007/ Accepted 4 December 2007

The intracellular parasite Leishmania causes a wide spectrum of human disease, ranging from self-resolving cutaneous lesions to fatal visceral disease, depending on the species of Leishmania involved. The mechanisms by which different Leishmania species cause different pathologies are largely unknown. We have addressed this question by comparing the gene expression profiles of bone marrow-derived macrophages infected with either Leishmania donovani or L. major promastigotes. We found that the two species had very similar effects on macrophage gene expression. Both species caused a small (<2.5-fold) but statistically significant repression of several hundred genes. In addition, both species strongly induced and repressed about 60 genes. Comparing the effects of the two species showed that only 26 genes were regulated differently by L. major as opposed to L. donovani, including those for metallothioneins 1 and 2, HSP70 and -72, CCL4, Gadd45β, Dsp1, matrix metalloprotease 13, T-cell death-associated gene 51 (Tdag51), RhoB, spermine/spermidine N1-acyl transferase 1 (SSAT), and Cox2. L. donovani-infected macrophages were also found to express higher levels of Cox2 protein and prostaglandin E synthase mRNA than L. major-infected macrophages. While both species have previously been shown to trigger prostaglandin E synthesis by bystander cells, this study suggests that infected macrophages themselves express prostaglandin E-synthesizing genes only in response to L. donovani.

Published ahead of print on 17 December 2007.

Supplemental material for this article may be found at http://iai.asm.org/.

Editor: W. A. Petri, Jr.

Present address: Department of Immunity and Infectious Disease, Harvard School of Public Health, 651 Huntington Avenue, Boston, MA 02115.