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To: tnsaf who wrote (1486)	2/10/2002 6:42:12 PM
From: tnsaf	Read Replies (1) \| Respond to of 7143

Human macrophage activation programs induced by bacterial pathogens Proc. Natl. Acad. Sci. USA, Vol. 99, Issue 3, 1503-1508, February 5, 2002 Gerard J. Nau,~, Joan F. L. Richmond, Ann Schlesinger, Ezra G. Jennings,§, Eric S. Lander,§, and Richard A. Young,§ * Whitehead Institute, 9 Cambridge Center, Cambridge, MA 02142; ~ Infectious Disease Unit, Massachusetts General Hospital, Boston, MA 02114; and § Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139 Understanding the response of innate immune cells to pathogens may provide insights to host defenses and the tactics used by pathogens to circumvent these defenses. We used DNA microarrays to explore the responses of human macrophages to a variety of bacteria. Macrophages responded to a broad range of bacteria with a robust, shared pattern of gene expression. The shared response includes genes encoding receptors, signal transduction molecules, and transcription factors. This shared activation program transforms the macrophage into a cell primed to interact with its environment and to mount an immune response. Further study revealed that the activation program is induced by bacterial components that are Toll-like receptor agonists, including lipopolysaccharide, lipoteichoic acid, muramyl dipeptide, and heat shock proteins. Pathogen-specific responses were also apparent in the macrophage expression profiles. Analysis of Mycobacterium tuberculosis-specific responses revealed inhibition of interleukin-12 production, suggesting one means by which this organism survives host defenses. These results improve our understanding of macrophage defenses, provide insights into mechanisms of pathogenesis, and suggest targets for therapeutic intervention. ------------------------------------------------------------ www.pnas.org/cgi/doi/10.1073/pnas.022649799 ------------------------------------------------------------ Another use of AFFX arrays. Jason